590 results on '"Blood Vessels immunology"'
Search Results
2. Non-classical monocytes have the support of the whole vascular tree.
- Author
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Minton K
- Subjects
- Humans, Animals, Blood Vessels immunology, Blood Vessels cytology, Mice, Monocytes immunology
- Published
- 2024
- Full Text
- View/download PDF
3. Integrin β1-mediated mast cell immune-surveillance of blood vessel content.
- Author
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Link K, Muhandes L, Polikarpova A, Lämmermann T, Sixt M, Fässler R, and Roers A
- Subjects
- Animals, Mice, Blood Vessels immunology, Mice, Knockout, Anaphylaxis immunology, Cell Degranulation immunology, Mice, Inbred C57BL, Skin immunology, Skin blood supply, Mast Cells immunology, Integrin beta1 immunology, Integrin beta1 metabolism, Integrin beta1 genetics, Immunoglobulin E immunology
- Abstract
Background: IgE-mediated degranulation of mast cells (MCs) provides rapid protection against environmental hazards, including animal venoms. A fraction of tissue-resident MCs intimately associates with blood vessels. These perivascular MCs were reported to extend projections into the vessel lumen and to be the first MCs to acquire intravenously injected IgE, suggesting that IgE loading of MCs depends on their vascular association., Objective: We sought to elucidate the molecular basis of the MC-blood vessel interaction and to determine its relevance for IgE-mediated immune responses., Methods: We selectively inactivated the Itgb1 gene, encoding the β1 chain of integrin adhesion molecules (ITGB1), in MCs by conditional gene targeting in mice. We analyzed skin MCs for blood vessel association, surface IgE density, and capability to bind circulating antibody specific for MC surface molecules, as well as in vivo responses to antigen administered via different routes., Results: Lack of ITGB1 expression severely compromised MC-blood vessel association. ITGB1-deficient MCs showed normal densities of surface IgE but reduced binding of intravenously injected antibodies. While their capacity to degranulate in response to IgE ligation in vivo was unimpaired, anaphylactic responses to antigen circulating in the vasculature were largely abolished., Conclusions: ITGB1-mediated association of MCs with blood vessels is key for MC immune surveillance of blood vessel content, but is dispensable for slow steady-state loading of endogenous IgE onto tissue-resident MCs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
4. An optical system for noninvasive microscopy of psoriatic mice in vivo.
- Author
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Lu Y, Zhu Y, Zhao X, Pan M, and He H
- Subjects
- Animals, Mice, Disease Models, Animal, Interleukin-23 blood, Interleukin-17 blood, Tumor Necrosis Factor-alpha blood, CD4-Positive T-Lymphocytes immunology, Blood Vessels diagnostic imaging, Blood Vessels immunology, Psoriasis blood, Psoriasis diagnostic imaging, Psoriasis immunology, Microscopy, Fluorescence methods, Skin diagnostic imaging, Skin immunology, Optical Imaging methods
- Abstract
Psoriasis is a chronic inflammatory skin disease involved with both complex morphological changes of skin and immune processes. The clinical diagnostics and research of psoriasis often require invasive biopsy which lacks their real-time dynamics in vivo. Here we report a noninvasive microscopic system developed by combining in vivo fluorescent microscopy, optical clearing, and immunolabeling to enable real-time imaging of immune cells and cytokines in blood flow in psoriatic animal models. The vascular morphology and time-lapse kinetics of interleukin (IL)-23, IL-17, tumor necrosis factor-α, and CD4+ cells in blood are captured at submicron resolution through the thickening epidermis and opaque scales during the development of psoriasis in vivo. Our data suggest IL-23 recruits CD4+ cells to release IL-17 in blood that further leaks out in the psoriatic skin area. This optical system enables noninvasive and real-time assessment of immune molecules and cells in vivo, providing good potential for medical researches on psoriasis., (© 2022 Wiley-VCH GmbH.)
- Published
- 2023
- Full Text
- View/download PDF
5. IL-18BP Improves Early Graft Function and Survival in Lewis-Brown Norway Rat Orthotopic Liver Transplantation Model.
- Author
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Meng Q, Wu W, Zhang W, Yuan J, Yang L, Zhang X, and Tao K
- Subjects
- Animals, Rats, Interferon-gamma genetics, Interferon-gamma metabolism, Rats, Inbred Lew, Genetic Vectors, Graft Rejection prevention & control, Interleukin-18 genetics, Interleukin-18 metabolism, Liver Transplantation methods, Graft Survival genetics, Genetic Therapy, Blood Vessels immunology
- Abstract
Interleukin-18 (IL-18) can effectively activate natural killer (NK) cells and induce large concentrations of interferon-γ (IFN-γ). In healthy humans, IL-18 binding protein (IL-18BP) can inhibit the binding of IL-18 to IL-18R and counteract the biological action of IL-18 due to its high concentration and high affinity, thus preventing the production of IFN-γ and inhibiting NK-cell activation. Through previous studies and the phenomena observed by our group in pig-non-human primates (NHPs) liver transplantation experiments, we proposed that the imbalance in IL-18/IL-18BP expression upon transplantation encourages the activation, proliferation, and cytotoxic effects of NK cells, ultimately causing acute vascular rejection of the graft. In this research, we used Lewis-Brown Norway rat orthotopic liver transplantation (OLTx) as a model of acute vascular rejection. AAV8-Il18bp viral vectors as gene delivery vehicles were constructed for gene therapy to overexpress IL-18BP and alleviate NK-cell rejection of the graft after transplantation. The results showed that livers overexpressing IL-18BP had reduced damage and could function longer after transplantation, effectively improving the survival time of the recipients.
- Published
- 2022
- Full Text
- View/download PDF
6. Pulmonary vascular inflammation with fatal coronavirus disease 2019 (COVID-19): possible role for the NLRP3 inflammasome.
- Author
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Paul O, Tao JQ, West E, Litzky L, Feldman M, Montone K, Rajapakse C, Bermudez C, and Chatterjee S
- Subjects
- Aged, Aged, 80 and over, Autopsy, Blood Vessels pathology, COVID-19 mortality, COVID-19 pathology, COVID-19 virology, Case-Control Studies, Female, Fluorescent Antibody Technique, Humans, Male, Middle Aged, Blood Vessels immunology, COVID-19 immunology, Inflammasomes analysis, Lung blood supply, NLR Family, Pyrin Domain-Containing 3 Protein analysis
- Abstract
Background: Pulmonary hyperinflammation is a key event with SARS-CoV-2 infection. Acute respiratory distress syndrome (ARDS) that often accompanies COVID-19 appears to have worse outcomes than ARDS from other causes. To date, numerous lung histological studies in cases of COVID-19 have shown extensive inflammation and injury, but the extent to which these are a COVID-19 specific, or are an ARDS and/or mechanical ventilation (MV) related phenomenon is not clear. Furthermore, while lung hyperinflammation with ARDS (COVID-19 or from other causes) has been well studied, there is scarce documentation of vascular inflammation in COVID-19 lungs., Methods: Lung sections from 8 COVID-19 affected and 11 non-COVID-19 subjects, of which 8 were acute respiratory disease syndrome (ARDS) affected (non-COVID-19 ARDS) and 3 were from subjects with non-respiratory diseases (non-COVID-19 non-ARDS) were H&E stained to ascertain histopathological features. Inflammation along the vessel wall was also monitored by expression of NLRP3 and caspase 1., Results: In lungs from COVID-19 affected subjects, vascular changes in the form of microthrombi in small vessels, arterial thrombosis, and organization were extensive as compared to lungs from non-COVID-19 (i.e., non-COVID-19 ARDS and non-COVID-19 non-ARDS) affected subjects. The expression of NLRP3 pathway components was higher in lungs from COVID-19 ARDS subjects as compared to non-COVID-19 non-ARDS cases. No differences were observed between COVID-19 ARDS and non-COVID-19 ARDS lungs., Conclusion: Vascular changes as well as NLRP3 inflammasome pathway activation were not different between COVID-19 and non-COVID-19 ARDS suggesting that these responses are not a COVID-19 specific phenomenon and are possibly more related to respiratory distress and associated strategies (such as MV) for treatment., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
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7. Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases.
- Author
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Kumar N, Saraber P, Ding Z, and Kusumbe AP
- Subjects
- Aging metabolism, Aging pathology, Animals, Arthritis, Rheumatoid immunology, Arthritis, Rheumatoid metabolism, Arthritis, Rheumatoid pathology, Blood Vessels metabolism, Blood Vessels pathology, Bone Diseases metabolism, Bone Diseases pathology, Bone Neoplasms immunology, Bone Neoplasms metabolism, Bone Neoplasms pathology, Cell Differentiation, Cell Proliferation, Endothelial Progenitor Cells immunology, Endothelial Progenitor Cells metabolism, Endothelial Progenitor Cells pathology, Hematopoietic Stem Cells metabolism, Hematopoietic Stem Cells pathology, Homeostasis, Humans, Osteoarthritis immunology, Osteoarthritis metabolism, Osteoarthritis pathology, Phenotype, Aging immunology, Blood Vessels immunology, Bone Diseases immunology, Bone and Bones blood supply, Hematopoietic Stem Cells immunology, Joints blood supply, Stem Cell Niche
- Abstract
The bones and joints in the skeletal system are composed of diverse cell types, including vascular niches, bone cells, connective tissue cells and mineral deposits and regulate whole-body homeostasis. The capacity of maintaining strength and generation of blood lineages lies within the skeletal system. Bone harbours blood and immune cells and their progenitors, and vascular cells provide several immune cell type niches. Blood vessels in bone are phenotypically and functionally diverse, with distinct capillary subtypes exhibiting striking changes with age. The bone vasculature has a special impact on osteogenesis and haematopoiesis, and dysregulation of the vasculature is associated with diverse blood and bone diseases. Ageing is associated with perturbed haematopoiesis, loss of osteogenesis, increased adipogenesis and diminished immune response and immune cell production. Endothelial and perivascular cells impact immune cell production and play a crucial role during inflammation. Here, we discuss normal and maladapted vascular niches in bone during development, homeostasis, ageing and bone diseases such as rheumatoid arthritis and osteoarthritis. Further, we discuss the role of vascular niches during bone malignancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kumar, Saraber, Ding and Kusumbe.)
- Published
- 2021
- Full Text
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8. Synapomorphic features of hepatic and pulmonary vasculatures include comparable purinergic signaling responses in host defense and modulation of inflammation.
- Author
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Hanidziar D and Robson SC
- Subjects
- Animals, Blood Vessels immunology, Humans, Liver blood supply, Lung blood supply, Purine Nucleotides metabolism, Blood Vessels metabolism, Liver metabolism, Lung metabolism, Receptors, Purinergic metabolism, Sepsis metabolism, Signal Transduction
- Abstract
Hepatosplanchnic and pulmonary vasculatures constitute synapomorphic, highly comparable networks integrated with the external environment. Given functionality related to obligatory requirements of "feeding and breathing," these organs are subject to constant environmental challenges entailing infectious risk, antigenic and xenobiotic exposures. Host responses to these stimuli need to be both protective and tightly regulated. These functions are facilitated by dualistic, high-low pressure blood supply of the liver and lungs, as well as tolerogenic characteristics of resident immune cells and signaling pathways. Dysregulation in hepatosplanchnic and pulmonary blood flow, immune responses, and microbiome implicate common pathogenic mechanisms across these vascular networks. Hepatosplanchnic diseases, such as cirrhosis and portal hypertension, often impact lungs and perturb pulmonary circulation and oxygenation. The reverse situation is also noted with lung disease resulting in hepatic dysfunction. Others, and we, have described common features of dysregulated cell signaling during liver and lung inflammation involving extracellular purines (e.g., ATP, ADP), either generated exogenously or endogenously. These metabokines serve as danger signals, when released by bacteria or during cellular stress and cause proinflammatory and prothrombotic signals in the gut/liver-lung vasculature. Dampening of these danger signals and organ protection largely depends upon activities of vascular and immune cell-expressed ectonucleotidases (CD39 and CD73), which convert ATP and ADP into anti-inflammatory adenosine. However, in many inflammatory disorders involving gut, liver, and lung, these protective mechanisms are compromised, causing perpetuation of tissue injury. We propose that interventions that specifically target aberrant purinergic signaling might prevent and/or ameliorate inflammatory disorders of the gut/liver and lung axis.
- Published
- 2021
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9. Combined Blockade of GARP:TGF-β1 and PD-1 Increases Infiltration of T Cells and Density of Pericyte-Covered GARP + Blood Vessels in Mouse MC38 Tumors.
- Author
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Bertrand C, Van Meerbeeck P, de Streel G, Vaherto-Bleeckx N, Benhaddi F, Rouaud L, Noël A, Coulie PG, van Baren N, and Lucas S
- Subjects
- Animals, Mice, Mice, Inbred BALB C, Antineoplastic Agents, Immunological immunology, Antineoplastic Agents, Immunological pharmacology, Blood Vessels immunology, Membrane Proteins antagonists & inhibitors, Membrane Proteins immunology, Neoplasms, Experimental blood supply, Neoplasms, Experimental drug therapy, Neoplasms, Experimental immunology, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic immunology, Pericytes immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, T-Lymphocytes, Regulatory immunology, Transforming Growth Factor beta1 antagonists & inhibitors, Transforming Growth Factor beta1 immunology
- Abstract
When combined with anti-PD-1, monoclonal antibodies (mAbs) against GARP:TGF-β1 complexes induced more frequent immune-mediated rejections of CT26 and MC38 murine tumors than anti-PD-1 alone. In both types of tumors, the activity of anti-GARP:TGF-β1 mAbs resulted from blocking active TGF-β1 production and immunosuppression by GARP-expressing regulatory T cells. In CT26 tumors, combined GARP:TGF-β1/PD-1 blockade did not augment the infiltration of T cells, but did increase the effector functions of already present anti-tumor T cells. Here we show that, in contrast, in MC38, combined GARP:TGF-β1/PD-1 blockade increased infiltration of T cells, as a result of increased extravasation of T cells from blood vessels. Unexpectedly, combined GARP:TGF-β1/PD-1 blockade also increased the density of GARP
+ blood vessels covered by pericytes in MC38, but not in CT26 tumors. This appears to occur because anti-GARP:TGF-β1, by blocking TGF-β1 signals, favors the proliferation of and expression of adhesion molecules such as E-selectin by blood endothelial cells. The resulting densification of intratumoral blood vasculature probably contributes to increased T cell infiltration and to the therapeutic efficacy of GARP:TGF-β1/PD-1 blockade in MC38. We conclude from these distinct observations in MC38 and CT26, that the combined blockades of GARP:TGF-β1 and PD-1 can exert anti-tumor activity via multiple mechanisms, including the densification and normalization of intratumoral blood vasculature, the increase of T cell infiltration into the tumor and the increase of the effector functions of intratumoral tumor-specific T cells. This may prove important for the selection of cancer patients who could benefit from combined GARP:TGF-β1/PD-1 blockade in the clinics., Competing Interests: Patents pertaining to results obtained with the 58A2 antibody clone (anti-mouse GARP:TGF-β1) have been filed under the Patent Cooperation Treaty (International application Number PCT/IB2019/053753), with SL, GS, PC as inventors and UCLouvain and argenx as applicants. SL received research support from argenx and owns stock options in argenx. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bertrand, Van Meerbeeck, de Streel, Vaherto-Bleeckx, Benhaddi, Rouaud, Noël, Coulie, van Baren and Lucas.)- Published
- 2021
- Full Text
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10. Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment.
- Author
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Ramos-Espinosa G, Wang Y, Brandner JM, Schneider SW, and Gorzelanny C
- Subjects
- Animals, Blood Vessels growth & development, Blood Vessels immunology, Blood Vessels pathology, Cell Line, Tumor, Endothelial Cells immunology, Endothelial Cells pathology, Endothelium, Vascular growth & development, Endothelium, Vascular immunology, Endothelium, Vascular pathology, Extracellular Matrix drug effects, Gene Expression Regulation, Neoplastic drug effects, Glycosaminoglycans pharmacology, HEK293 Cells, Human Umbilical Vein Endothelial Cells, Humans, Melanoma immunology, Melanoma pathology, Microfluidic Analytical Techniques, Neovascularization, Pathologic immunology, Neovascularization, Pathologic pathology, Protein Binding genetics, Protein Binding immunology, Chemokine CCL2 genetics, Chitinase-3-Like Protein 1 genetics, Melanoma genetics, Neovascularization, Pathologic genetics, Vascular Endothelial Growth Factor A genetics
- Abstract
Chitinase 3-like 1 (CHI3L1) is an enzymatically inactive mammalian chitinase that is associated with tumor inflammation. Previous research indicated that CHI3L1 is able to interact with different extracellular matrix components, such as heparan sulfate. In the present work, we investigated whether the interaction of CHI3L1 with the extracellular matrix of melanoma cells can trigger an inflammatory activation of endothelial cells. The analysis of the melanoma cell secretome indicated that CHI3L1 increases the abundance of various cytokines, such as CC-chemokine ligand 2 (CCL2), and growth factors, such as vascular endothelial growth factor A (VEGF-A). Using a solid-phase binding assay, we found that heparan sulfate-bound VEGF-A and CCL2 were displaced by recombinant CHI3L1 in a dose-dependent manner. Microfluidic experiments indicated that the CHI3L1 altered melanoma cell secretome promoted immune cell recruitment to the vascular endothelium. In line with the elevated VEGF-A levels, CHI3L1 was also able to promote angiogenesis through the release of extracellular matrix-bound pro-angiogenic factors. In conclusion, we showed that CHI3L1 is able to affect the tumor cell secretome, which in turn can regulate immune cell recruitment and blood vessel formation. Accordingly, our data suggest that the molecular targeting of CHI3L1 in the course of cancer immunotherapies can tune patients' response and antitumoral inflammation.
- Published
- 2021
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11. Macrophage-Mediated Tissue Vascularization: Similarities and Differences Between Cornea and Skin.
- Author
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Hadrian K, Willenborg S, Bock F, Cursiefen C, Eming SA, and Hos D
- Subjects
- Animals, Blood Vessels immunology, Blood Vessels pathology, Humans, Lymphatic Vessels immunology, Lymphatic Vessels pathology, Macrophages immunology, Macrophages pathology, Phenotype, Signal Transduction, Wound Healing, Blood Vessels metabolism, Cornea blood supply, Corneal Neovascularization, Lymphangiogenesis, Lymphatic Vessels metabolism, Macrophages metabolism, Neovascularization, Physiologic, Skin blood supply
- Abstract
Macrophages are critical mediators of tissue vascularization both in health and disease. In multiple tissues, macrophages have been identified as important regulators of both blood and lymphatic vessel growth, specifically following tissue injury and in pathological inflammatory responses. In development, macrophages have also been implicated in limiting vascular growth. Hence, macrophages provide an important therapeutic target to modulate tissue vascularization in the clinic. However, the molecular mechanisms how macrophages mediate tissue vascularization are still not entirely resolved. Furthermore, mechanisms might also vary among different tissues. Here we review the role of macrophages in tissue vascularization with a focus on their role in blood and lymphatic vessel formation in the barrier tissues cornea and skin. Comparing mechanisms of macrophage-mediated hem- and lymphangiogenesis in the angiogenically privileged cornea and the physiologically vascularized skin provides an opportunity to highlight similarities but also tissue-specific differences, and to understand how macrophage-mediated hem- and lymphangiogenesis can be exploited for the treatment of disease, including corneal wound healing after injury, graft rejection after corneal transplantation or pathological vascularization of the skin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hadrian, Willenborg, Bock, Cursiefen, Eming and Hos.)
- Published
- 2021
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12. Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation.
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Dudeck J, Kotrba J, Immler R, Hoffmann A, Voss M, Alexaki VI, Morton L, Jahn SR, Katsoulis-Dimitriou K, Winzer S, Kollias G, Fischer T, Nedospasov SA, Dunay IR, Chavakis T, Müller AJ, Schraven B, Sperandio M, and Dudeck A
- Subjects
- Animals, Blood Circulation, Cell Degranulation, Cells, Cultured, Immune System Diseases, Leukocyte Disorders, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophil Activation, Receptors, Tumor Necrosis Factor, Type I metabolism, Secretory Vesicles metabolism, Tumor Necrosis Factor-alpha genetics, Blood Vessels immunology, Dermatitis, Contact immunology, Inflammation immunology, Mast Cells immunology, Neutrophils immunology, Skin pathology, Tumor Necrosis Factor-alpha metabolism
- Abstract
Tissue resident mast cells (MCs) rapidly initiate neutrophil infiltration upon inflammatory insult, yet the molecular mechanism is still unknown. Here, we demonstrated that MC-derived tumor necrosis factor (TNF) was crucial for neutrophil extravasation to sites of contact hypersensitivity-induced skin inflammation by promoting intraluminal crawling. MC-derived TNF directly primed circulating neutrophils via TNF receptor-1 (TNFR1) while being dispensable for endothelial cell activation. The MC-derived TNF was infused into the bloodstream by directional degranulation of perivascular MCs that were part of the vascular unit with access to the vessel lumen. Consistently, intravenous administration of MC granules boosted neutrophil extravasation. Pronounced and rapid intravascular MC degranulation was also observed upon IgE crosslinking or LPs challenge indicating a universal MC potential. Consequently, the directional MC degranulation of pro-inflammatory mediators into the bloodstream may represent an important target for therapeutic approaches aimed at dampening cytokine storm syndromes or shock symptoms, or intentionally pushing immune defense., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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13. The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein.
- Author
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Yusuf B, Mukovozov I, Patel S, Huang YW, Liu GY, Reddy EC, Skrtic M, Glogauer M, and Robinson LA
- Subjects
- Animals, Atherosclerosis immunology, Atherosclerosis pathology, Blood Vessels immunology, CD36 Antigens genetics, CD36 Antigens immunology, Disease Models, Animal, Foam Cells, Humans, Intercellular Signaling Peptides and Proteins metabolism, Lipids genetics, Lipoproteins, LDL immunology, Macrophages immunology, Mice, Monocytes immunology, Nerve Tissue Proteins metabolism, Receptors, Scavenger genetics, Receptors, Scavenger immunology, Atherosclerosis genetics, Intercellular Signaling Peptides and Proteins genetics, Lipids immunology, Lipoproteins, LDL genetics, Nerve Tissue Proteins genetics
- Abstract
Atherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.
- Published
- 2021
- Full Text
- View/download PDF
14. Rogue antibodies could be driving severe COVID-19.
- Author
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Khamsi R
- Subjects
- Aging immunology, Annexin A2 immunology, Autoantibodies isolation & purification, Autoimmune Diseases microbiology, Autoimmune Diseases virology, B-Lymphocytes immunology, B-Lymphocytes pathology, Blood Coagulation immunology, Blood Vessels immunology, Blood Vessels pathology, Brain immunology, Brain pathology, COVID-19 etiology, COVID-19 immunology, COVID-19 pathology, COVID-19 virology, Critical Illness, Cytokine Release Syndrome complications, Cytokine Release Syndrome immunology, Cytokine Release Syndrome pathology, Cytokine Release Syndrome physiopathology, Female, HLA-DRB1 Chains immunology, Helicobacter pylori immunology, Helicobacter pylori pathogenicity, Herpesvirus 4, Human immunology, Herpesvirus 4, Human pathogenicity, Humans, Interferon Type I antagonists & inhibitors, Interferon Type I immunology, Male, Myocardium immunology, Myocardium pathology, Phospholipids immunology, Racial Groups, SARS-CoV-2 immunology, SARS-CoV-2 isolation & purification, Sex Characteristics, Streptococcus pyogenes immunology, Streptococcus pyogenes pathogenicity, Time Factors, Post-Acute COVID-19 Syndrome, Autoantibodies adverse effects, Autoantibodies immunology, Autoimmune Diseases etiology, Autoimmune Diseases immunology, COVID-19 complications, COVID-19 physiopathology, Models, Immunological, SARS-CoV-2 pathogenicity
- Published
- 2021
- Full Text
- View/download PDF
15. Activated melanoma vessels: A sticky point for successful immunotherapy.
- Author
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Weishaupt C, Goerge T, and Loser K
- Subjects
- Animals, Blood Vessels immunology, Cell Movement, Disease Models, Animal, Humans, Melanoma blood supply, Melanoma immunology, Melanoma secondary, Mice, Receptors, Lymphocyte Homing, Skin Neoplasms blood supply, Skin Neoplasms immunology, Skin Neoplasms pathology, Tumor Escape immunology, Endothelium immunology, Immunotherapy, Lymphocytes immunology, Melanoma therapy, Skin Neoplasms therapy
- Abstract
Metastatic melanoma is a devastating disease with a marginal-albeit increasing-hope for cure. Melanoma has a high mutation rate which correlates to the expression of numerous neo-antigens and thus is associated with the potential to induce and strengthen effective antitumoral immunity. However, the incomplete and potentially insufficient response to established immunotherapies (response rates usually do not markedly exceed 60%) already points to the need of further studies to improve treatment strategies. Multiple tumor escape mechanisms that allow melanoma to evade from antitumoral immune responses have been characterized and must be overcome to achieve a better clinical efficacy of immunotherapies. Recently, promising progress has been made in targeting tumor vasculature to control and increase the infiltration of tumors with effector lymphocytes. It has been hypothesized that amplified lymphocytic infiltrates in melanoma metastases result in a switch of the tumor microenvironment from a non-inflammatory to an inflammatory state. In this view point essay, we discuss the requirements for successful homing of lymphocytes to melanoma tissue and we present a mouse melanoma xenograft model that allows the investigation of human tumor vessels in vivo. Furthermore, current clinical studies dealing with the activation of melanoma vasculature for enhanced effectiveness of immunotherapy protocols are presented and open questions for routine clinical application are addressed., (© 2020 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
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16. COVID-19: Are we dealing with a multisystem vasculopathy in disguise of a viral infection?
- Author
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Mondal R, Lahiri D, Deb S, Bandyopadhyay D, Shome G, Sarkar S, Paria SR, Thakurta TG, Singla P, and Biswas SC
- Subjects
- Animals, Betacoronavirus genetics, Betacoronavirus immunology, Blood Coagulation, Blood Vessels immunology, Blood Vessels metabolism, Blood Vessels physiopathology, COVID-19, Coronavirus Infections immunology, Coronavirus Infections metabolism, Coronavirus Infections physiopathology, Cytokines metabolism, Hemodynamics, Host-Pathogen Interactions, Humans, Inflammation Mediators metabolism, Pandemics, Phylogeny, Pneumonia, Viral immunology, Pneumonia, Viral metabolism, Pneumonia, Viral physiopathology, Prognosis, Risk Assessment, Risk Factors, SARS-CoV-2, Vascular Diseases immunology, Vascular Diseases metabolism, Vascular Diseases physiopathology, Betacoronavirus pathogenicity, Blood Vessels virology, Coronavirus Infections virology, Pneumonia, Viral virology, Vascular Diseases virology
- Abstract
After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic with unprecedented global response. With the expanding domain of presentations in COVID-19 patients, the full range of manifestations is yet to unfold. The classical clinical symptoms for SARS-CoV-2 affected patients are dry cough, high fever, dyspnoea, lethal pneumonia whereas many patients have also been found to be associated with a few additional signs and clinical manifestations of isolated vasculopathy. Albeit a deep and profound knowledge has been gained on the clinical features and management of COVID-19, less clear association has been provided on SARS-CoV-2 mediated direct or indirect vasculopathy and its possible correlation with disease prognosis. The accumulative evidences suggest that novel coronavirus, apart from its primary respiratory confinement, may also invade vascular endothelial cells of several systems including cerebral, cardio-pulmonary as well as renal microvasculature, modulating multiple visceral perfusion indices. Here we analyse the phylogenetic perspective of SARS-CoV-2 along with other strains of β-coronaviridae from a standpoint of vasculopathic derangements. Based on the existing case reports, literature and open data bases, we also analyse the differential pattern of vasculopathy related changes in COVID-19 positive patients. Besides, we debate the need of modulation in clinical approach from a hemodynamical point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV-2 affected patients.
- Published
- 2020
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17. COVID-19-associated vasculitis and vasculopathy.
- Author
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Becker RC
- Subjects
- Animals, Betacoronavirus immunology, Blood Coagulation, Blood Vessels immunology, Blood Vessels pathology, Blood Vessels physiopathology, COVID-19, Coronavirus Infections diagnosis, Coronavirus Infections immunology, Coronavirus Infections physiopathology, Host-Pathogen Interactions, Humans, Inflammation Mediators blood, Pandemics, Pneumonia, Viral diagnosis, Pneumonia, Viral immunology, Pneumonia, Viral physiopathology, Prognosis, Risk Factors, SARS-CoV-2, Vasculitis diagnosis, Vasculitis immunology, Vasculitis physiopathology, Betacoronavirus pathogenicity, Blood Vessels virology, Coronavirus Infections virology, Pneumonia, Viral virology, Vasculitis virology
- Abstract
The COVID-19 pandemic now totaling 13,000,000 cases and over 571,000 deaths has continued to teach the medical, scientific and lay communities about viral infectious disease in the modern era. Among the many lessons learned for the medical community is the potential for transmissibility and host infectivity of the SARS-CoV-2 virus. Moreover, it has become clear that the virus can affect any organ including the circulatory system, directly via either tissue tropism or indirectly stemming from inflammatory responses in the form of innate immunity, leukocyte debris such as cell-free DNA and histones and RNA viral particles. The following review considers COVID-19-associated vasculitis and vasculopathy as a defining feature of a virus-induced systemic disease with acute, subacute and potential chronic health implications.
- Published
- 2020
- Full Text
- View/download PDF
18. Hemostasis vs. homeostasis: Platelets are essential for preserving vascular barrier function in the absence of injury or inflammation.
- Author
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Gupta S, Konradt C, Corken A, Ware J, Nieswandt B, Di Paola J, Yu M, Wang D, Nieman MT, Whiteheart SW, and Brass LF
- Subjects
- Animals, Blood Vessels injuries, Blood Vessels physiopathology, Female, Lectins, C-Type genetics, Lectins, C-Type immunology, Male, Meninges blood supply, Meninges immunology, Mice, Phospholipase C gamma genetics, Phospholipase C gamma immunology, Skin blood supply, Skin immunology, Blood Platelets immunology, Blood Vessels immunology, Hemostasis, Homeostasis
- Abstract
Platelets are best known for their vasoprotective responses to injury and inflammation. Here, we have asked whether they also support vascular integrity when neither injury nor inflammation is present. Changes in vascular barrier function in dermal and meningeal vessels were measured in real time in mouse models using the differential extravasation of fluorescent tracers as a biomarker. Severe thrombocytopenia produced by two distinct methods caused increased extravasation of 40-kDa dextran from capillaries and postcapillary venules but had no effect on extravasation of 70-kDa dextran or albumin. This reduction in barrier function required more than 4 h to emerge after thrombocytopenia was established, reverting to normal as the platelet count recovered. Barrier dysfunction was also observed in mice that lacked platelet-dense granules, dense granule secretion machinery, glycoprotein (GP) VI, or the GPVI signaling effector phospholipase C (PLC) γ2. It did not occur in mice lacking α-granules, C type lectin receptor-2 (CLEC-2), or protease activated receptor 4 (PAR4). Notably, although both meningeal and dermal vessels were affected, intracerebral vessels, which are known for their tighter junctions between endothelial cells, were not. Collectively, these observations 1) highlight a role for platelets in maintaining vascular homeostasis in the absence of injury or inflammation, 2) provide a sensitive biomarker for detecting changes in platelet-dependent barrier function, 3) identify which platelet processes are required, and 4) suggest that the absence of competent platelets causes changes in the vessel wall itself, accounting for the time required for dysfunction to emerge., Competing Interests: The authors declare no competing interest.
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- 2020
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19. Macrophage TLR4 and PAR2 Signaling: Role in Regulating Vascular Inflammatory Injury and Repair.
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Rayees S, Rochford I, Joshi JC, Joshi B, Banerjee S, and Mehta D
- Subjects
- Acute Lung Injury pathology, Animals, Blood Vessels injuries, Blood Vessels pathology, Capillary Permeability immunology, Humans, Lung blood supply, Macrophages pathology, Acute Lung Injury immunology, Blood Vessels immunology, Lung immunology, Macrophages immunology, Receptor, PAR-2 immunology, Signal Transduction immunology, Toll-Like Receptor 4 immunology
- Abstract
Macrophages play a central role in dictating the tissue response to infection and orchestrating subsequent repair of the damage. In this context, macrophages residing in the lungs continuously sense and discriminate among a wide range of insults to initiate the immune responses important to host-defense. Inflammatory tissue injury also leads to activation of proteases, and thereby the coagulation pathway, to optimize injury and repair post-infection. However, long-lasting inflammatory triggers from macrophages can impair the lung's ability to recover from severe injury, leading to increased lung vascular permeability and neutrophilic injury, hallmarks of Acute Lung Injury (ALI). In this review, we discuss the roles of toll-like receptor 4 (TLR4) and protease activating receptor 2 (PAR2) expressed on the macrophage cell-surface in regulating lung vascular inflammatory signaling., (Copyright © 2020 Rayees, Rochford, Joshi, Joshi, Banerjee and Mehta.)
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- 2020
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20. Can Glycine Mitigate COVID-19 Associated Tissue Damage and Cytokine Storm?
- Author
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Li CY
- Subjects
- Betacoronavirus drug effects, Betacoronavirus pathogenicity, Blood Vessels immunology, Blood Vessels virology, Brain immunology, Brain virology, COVID-19, Coronavirus Infections genetics, Coronavirus Infections metabolism, Coronavirus Infections virology, Cytokines drug effects, Cytokines genetics, Glycine genetics, Glycine therapeutic use, Heart virology, Humans, Intestines immunology, Intestines virology, Kidney immunology, Kidney virology, Liver immunology, Liver virology, Lung immunology, Lung virology, Pandemics, Pneumonia, Viral genetics, Pneumonia, Viral metabolism, Pneumonia, Viral virology, SARS-CoV-2, Coronavirus Infections therapy, Cytokines biosynthesis, Glycine metabolism, Pneumonia, Viral therapy
- Published
- 2020
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21. A plea for the pathogenic role of immune complexes in severe Covid-19.
- Author
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Vuitton DA, Vuitton L, Seillès E, and Galanaud P
- Subjects
- Antibodies, Viral biosynthesis, Antigen-Antibody Complex drug effects, Betacoronavirus immunology, Blood Vessels drug effects, Blood Vessels immunology, Blood Vessels pathology, Blood Vessels virology, COVID-19, Complement C3 antagonists & inhibitors, Complement C3 biosynthesis, Complement Inactivating Agents therapeutic use, Coronavirus Infections complications, Coronavirus Infections drug therapy, Coronavirus Infections virology, Cytokine Release Syndrome complications, Cytokine Release Syndrome drug therapy, Cytokine Release Syndrome virology, Humans, Immune Complex Diseases complications, Immune Complex Diseases drug therapy, Immune Complex Diseases virology, Immunity, Humoral drug effects, Interleukin 1 Receptor Antagonist Protein therapeutic use, Interleukin-6 antagonists & inhibitors, Interleukin-6 biosynthesis, Pandemics, Pneumonia, Viral complications, Pneumonia, Viral drug therapy, Pneumonia, Viral virology, Receptors, Interleukin-1 antagonists & inhibitors, Receptors, Interleukin-1 biosynthesis, SARS-CoV-2, Severe Acute Respiratory Syndrome complications, Severe Acute Respiratory Syndrome drug therapy, Severe Acute Respiratory Syndrome virology, Severity of Illness Index, Vasculitis complications, Vasculitis drug therapy, Vasculitis virology, Antigen-Antibody Complex biosynthesis, Betacoronavirus pathogenicity, Coronavirus Infections immunology, Cytokine Release Syndrome immunology, Immune Complex Diseases immunology, Pneumonia, Viral immunology, Severe Acute Respiratory Syndrome immunology, Vasculitis immunology
- Abstract
Competing Interests: Declaration of Competing Interest None.
- Published
- 2020
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22. Type 3 hypersensitivity in COVID-19 vasculitis.
- Author
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Roncati L, Ligabue G, Fabbiani L, Malagoli C, Gallo G, Lusenti B, Nasillo V, Manenti A, and Maiorana A
- Subjects
- Aged, Antibodies, Viral biosynthesis, Antigen-Antibody Complex biosynthesis, Betacoronavirus immunology, Blood Vessels immunology, Blood Vessels pathology, Blood Vessels virology, COVID-19, Complement C3 biosynthesis, Coronavirus Infections complications, Coronavirus Infections virology, Cytokine Release Syndrome complications, Cytokine Release Syndrome virology, Disease Progression, Endothelial Cells immunology, Endothelial Cells pathology, Endothelial Cells virology, Humans, Immune Complex Diseases complications, Immune Complex Diseases virology, Immunity, Humoral, Immunoglobulin G biosynthesis, Immunoglobulin M biosynthesis, Interleukin-6 biosynthesis, Male, Pandemics, Pneumonia, Viral complications, Pneumonia, Viral virology, SARS-CoV-2, Severe Acute Respiratory Syndrome complications, Severe Acute Respiratory Syndrome virology, Th2 Cells pathology, Th2 Cells virology, Vasculitis complications, Vasculitis virology, Betacoronavirus pathogenicity, Coronavirus Infections immunology, Cytokine Release Syndrome immunology, Immune Complex Diseases immunology, Pneumonia, Viral immunology, Severe Acute Respiratory Syndrome immunology, Th2 Cells immunology, Vasculitis immunology
- Abstract
Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels., Competing Interests: Declaration of Competing Interest None of the authors has any financial conflict of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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23. A Phase IV, Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Effects of Ustekinumab on Vascular Inflammation in Psoriasis (the VIP-U Trial).
- Author
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Gelfand JM, Shin DB, Alavi A, Torigian DA, Werner T, Papadopoulos M, Takeshita J, Noe MH, Dey AK, Playford MP, and Mehta NN
- Subjects
- Biomarkers metabolism, Cross-Over Studies, Cytokines metabolism, Double-Blind Method, Follow-Up Studies, Inflammation Mediators metabolism, Interleukin-12 antagonists & inhibitors, Interleukin-23 antagonists & inhibitors, Placebos, Anti-Inflammatory Agents therapeutic use, Blood Vessels immunology, Inflammation drug therapy, Psoriasis drug therapy, Th17 Cells immunology, Ustekinumab therapeutic use
- Abstract
Psoriasis is a T helper type 17 autoimmune disease associated with an increased risk cardiovascular events and mortality. Ustekinumab, an antibody to p40, blocks cytokines IL-12 and IL-23, and is a highly effective and safe treatment for psoriasis. We conducted a randomized double-blinded placebo-controlled trial to determine the effect of ustekinumab on aortic vascular inflammation (AVI) measured by imaging, and key biomarkers of inflammation, lipid, and glucose metabolism in the blood of patients with moderate-to-severe psoriasis. A total of 43 patients were randomized, and at week 12, ustekinumab-treated patients had a -18.65% (95% confidence interval = -29.45% to -7.85%) reduction in AVI, a reduction in inflammatory biomarkers, and an increase in apolipoprotein B lipoproteins compared with placebo. At week 12, placebo patients were crossed over such that all patients received ustekinumab for 52 weeks. At the end of 52 weeks of ustekinumab treatment, there was no change in AVI compared with baseline, inflammatory markers were reduced, and there were increases in selected measures of lipids and leptin. These results show that blockade of IL-12 and/or IL-23 may transiently reduce AVI, with more durable reduction in inflammatory cytokines associated with cardiovascular disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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24. [Vascular Remodeling Induced by Biological Stresses].
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Hasegawa H
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Humans, Mice, Prostaglandins metabolism, Prostaglandins physiology, Stress, Physiological physiology, T-Lymphocytes immunology, Thymus Gland pathology, Blood Vessels immunology, Blood Vessels physiopathology, Stress, Physiological immunology, Stress, Psychological immunology, Thymus Gland immunology, Vascular Remodeling drug effects
- Abstract
The thymus is a vital organ for functional immune systems, and is the site of T cell development, which plays a central role in cellular immune defenses. Unlike other major organs, the thymus is highly dynamic in size and structure. It shrinks immediately upon bacterial infection, aging, pregnancy, mental stress, nutritional deficiency, and more. The reduction in size and function of the thymus during such biological events is called thymic involution or thymic atrophy; thymic involution is a particularly important issue because dysfunctional T cell immunity increases the risks of tumorigenesis and infectious diseases. However, the molecular mechanisms underlying thymic involution remain obscure. Our recent study indicated that blood vessels are remodeled during thymic involution that occurs upon aging, estradiol-treatment, or nutritional deficiency. We also found that prostanoid synthesis is induced during thymic involution. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs), aspirin or etodolac, at least partially inhibited thymic involution-induced remodeling of the blood vessels, suggesting that prostanoids are involved in blood vessel remodeling. Our results revealed the potential role of blood vessel remodeling during thymic involution, which can lead to biological stress-induced immunosenescence.
- Published
- 2020
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25. Treating the Different Phenotypes of Behçet's Syndrome.
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Bettiol A, Hatemi G, Vannozzi L, Barilaro A, Prisco D, and Emmi G
- Subjects
- Behcet Syndrome etiology, Blood Vessels immunology, Blood Vessels metabolism, Blood Vessels pathology, Cartilage, Articular immunology, Cartilage, Articular metabolism, Cartilage, Articular pathology, Combined Modality Therapy, Disease Management, Humans, Mucous Membrane immunology, Mucous Membrane metabolism, Mucous Membrane pathology, Behcet Syndrome diagnosis, Behcet Syndrome therapy, Phenotype
- Abstract
Behçet's syndrome (BS) is a multisystemic vasculitis, characterized by different clinical involvements, including mucocutaneous, ocular, vascular, neurological, and gastrointestinal manifestations. Based on this heterogeneity, BS can be hardly considered as a single clinical entity. Growing evidence supports that, within BS, different phenotypes, characterized by clusters of co-existing involvements, can be distinguished. Namely, three major BS phenotypes have been reported: (a) the mucocutaneous and articular phenotype, (b) the extra-parenchymal neurological and peripheral vascular phenotype, and (c) the parenchymal neurological and ocular phenotype. To date, guidelines for the management of BS have been focused on the pharmacological treatment of each specific BS manifestation. However, tailoring the treatments on patient's specific phenotype, rather than on single disease manifestation, could represent a valid strategy for a personalized therapeutic approach to BS. In the present literature review, we summarize current evidence on the pharmacological treatments for the first-, second-, and third-line treatment of the major BS phenotypes., (Copyright © 2019 Bettiol, Hatemi, Vannozzi, Barilaro, Prisco and Emmi.)
- Published
- 2019
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26. IL-10 IS DOWN-REGULATED IN THE CARDIOVASCULAR DISEASES SUSPECTED PATIENTS, INDEPENDENT OF ANGIOGRAPHY.
- Author
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Razavi S, Ahmadi-Roknabadi F, Safarian M, Mehdipour A, Anbarian A, Mirzamohammadi M, Zeinali M, and Kazemi Arababadi M
- Subjects
- Angiocardiography, Blood Vessels diagnostic imaging, Blood Vessels immunology, Blood Vessels pathology, Cardiovascular Diseases genetics, Cardiovascular Diseases immunology, Cardiovascular Diseases pathology, Case-Control Studies, Cigarette Smoking physiopathology, Constriction, Pathologic genetics, Constriction, Pathologic immunology, Constriction, Pathologic pathology, Female, Humans, Interferon-gamma blood, Interferon-gamma immunology, Interleukin-10 blood, Interleukin-10 immunology, Male, Middle Aged, Opium Dependence physiopathology, Risk Factors, X-Rays, Cardiovascular Diseases diagnostic imaging, Constriction, Pathologic diagnostic imaging, Gene Expression Regulation radiation effects, Interferon-gamma genetics, Interleukin-10 genetics
- Abstract
IL-10 and interferon-gamma (IFN-γ) are the important anti and pro-inflammatory cytokines, respectively, which may participate in the cardiovascular disease pathogenesis. Additionally, environmental factors, such as the X-ray, can modulate cytokine expression. Due to the fact that X-ray is used during angiography, hence, angiography may alter expression of the cytokines., Objective: Accordingly, this project was aimed to assess IL-10 and IFN-γ serum levels within cardiovascular patients (with and without vessel stenosis) versus healthy controls and also the effects of angiography on the serum levels of the cytokines., Material and Methods: This study was performed on the 80 participants, including twenty cases in each group (healthy controls and cardiovascular patients without vessel stenosis, stenosis of 1 vessel and stenosis of more than 1 vessel) to evaluate IL-10 and IFN-γ serum levels using ELISA technique. The IL-10 and IFN-γ serum levels also compared within group 2, 3 and 4 before and after angiography to explore the effects of the technique on the IL-10 and IFN-γ serum levels., Results: IL-10, but not IFN-γ, serum levels were higher in the healthy controls than all cardiovascular patients. IL-10 and IFN-γ serum levels were not altered after angiography and also were not differ in the smoker versus non- smoker and opium consuming versus non-opium consuming participants., Conclusion: Due to the results it may be concluded that IL-10 can be considered as a plausible inhibitor of cardio- vascular diseases independent of angiography duration and X-ray, however, IFN-γ has no effects in the Iranian patients suffering from cardiovascular diseases., (S. Razavi, F. Ahmadi-Roknabadi, M. Safarian, A. Mehdipour, A. Anbarian, M. Mirzamohammadi, M. Zeinali, M. Kazemi Arababadi.)
- Published
- 2019
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27. Snake venom rhodocytin induces plasma extravasation via toxin-mediated interactions between platelets and mast cells.
- Author
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Nakamura Y, Sasaki T, Mochizuki C, Ishimaru K, Koizumi S, Shinmori H, Suzuki-Inoue K, and Nakao A
- Subjects
- Adenosine Triphosphate metabolism, Biomarkers, Blood Vessels drug effects, Blood Vessels immunology, Blood Vessels metabolism, Edema pathology, Gene Expression, Histamine metabolism, Platelet Activation drug effects, Receptors, Purinergic P2X7 metabolism, Signal Transduction drug effects, Skin immunology, Skin metabolism, Skin pathology, Viper Venoms pharmacology, Blood Platelets metabolism, Cell Communication drug effects, Edema etiology, Edema metabolism, Mast Cells metabolism, Viper Venoms toxicity
- Abstract
Venomous snakebites can induce local tissue damage, including necrosis of soft tissues, haemorrhage, blistering and local swelling associated with plasma extravasation, which can lead to lethal complications such as hypovolemic shock. However, the details of the underlying mechanisms remain unknown. In this study, we showed that intradermal treatment of mice with venom rhodocytin from the Malayan viper Calloselasma rhodostoma induced plasma extravasation, dependent on C-type lectin-like receptor 2 (CLEC-2) on platelets. Rhodocytin-induced plasma extravasation also relied on mast cells and histamine. In vitro co-culture of rhodocytin-activated platelets with mast cells induced histamine release from mast cells in an ATP/P2X7-dependent manner. Consistent with this, blockade or deficiency of P2X7 in mast cells suppressed rhodocytin-induced plasma extravasation in the skin. Together, these findings indicate that rhodocytin induces plasma extravasation by triggering platelet activation via CLEC-2, followed by activation of mast cells and histamine release via the ATP/P2X7 pathway. These results reveal a previously unrecognized mechanism by which snake venom increases vascular permeability via complex venom toxin-mediated interactions between platelets and mast cells.
- Published
- 2019
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28. Gateway reflex: Local neuroimmune interactions that regulate blood vessels.
- Author
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Kamimura D, Ohki T, Arima Y, Ota M, and Murakami M
- Subjects
- Animals, Blood Vessels metabolism, Blood-Brain Barrier metabolism, Humans, Inflammation Mediators metabolism, Pain immunology, Pain metabolism, Blood Vessels immunology, Blood-Brain Barrier immunology, Inflammation Mediators immunology, Neuroimmunomodulation physiology, Reflex physiology
- Abstract
Neuroimmunology is a research field that intersects neuroscience and immunology, with the larger aim of gaining significant insights into the pathophysiology of chronic inflammatory diseases such as multiple sclerosis. Conventional studies in this field have so far mainly dealt with immune responses in the nervous system (i.e. neuroinflammation) or systemic immune regulation by the release of glucocorticoids. On the other hand, recently accumulating evidence has indicated bidirectional interactions between specific neural activations and local immune responses. Here we discuss one such local neuroimmune interaction, the gateway reflex. The gateway reflex represents a mechanism that translates specific neural stimulations into local inflammatory outcomes by changing the state of specific blood vessels to allow immune cells to extravasate, thus forming the gateway. Several types of gateway reflex have been identified, and each regulates distinct blood vessels to create gateways for immune cells that induce local inflammation. The gateway reflex represents a novel therapeutic strategy for neuroinflammation and is potentially applicable to other inflammatory diseases in peripheral organs., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2019
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29. The Dual Role of Surfactant Protein-D in Vascular Inflammation and Development of Cardiovascular Disease.
- Author
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Colmorten KB, Nexoe AB, and Sorensen GL
- Subjects
- Animals, Atherosclerosis metabolism, Blood Vessels metabolism, Blood Vessels pathology, Cardiovascular Diseases metabolism, Inflammation metabolism, Interferon-gamma immunology, Interferon-gamma metabolism, Mice, Pulmonary Surfactant-Associated Protein D metabolism, Risk Factors, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Atherosclerosis immunology, Blood Vessels immunology, Cardiovascular Diseases immunology, Inflammation immunology, Pulmonary Surfactant-Associated Protein D immunology
- Abstract
Cardiovascular disease (CVD) is responsible for 31% of all global deaths. Atherosclerosis is the major cause of cardiovascular disease and is a chronic inflammatory disorder in the arteries. Atherosclerosis is characterized by the accumulation of cholesterol, extracellular matrix, and immune cells in the vascular wall. Recently, the collectin surfactant protein-D (SP-D), an important regulator of the pulmonary immune response, was found to be expressed in the vasculature. Several in vitro studies have examined the role of SP-D in the vascular inflammation leading to atherosclerosis. These studies show that SP-D plays a dual role in the development of atherosclerosis. In general, SP-D shows anti-inflammatory properties, and dampens local inflammation in the vessel, as well as systemic inflammation. However, SP-D can also exert a pro-inflammatory role, as it stimulates C-C chemokine receptor 2 inflammatory blood monocytes to secrete tumor necrosis-factor α and increases secretion of interferon-γ from natural killer cells. In vivo studies examining the role of SP-D in the development of atherosclerosis agree that SP-D plays a proatherogenic role, with SP-D knockout mice having smaller atherosclerotic plaque areas, which might be caused by a decreased systemic inflammation. Clinical studies examining the association between SP-D and cardiovascular disease have reported a positive association between circulatory SP-D level, carotid intima-media thickness, and coronary artery calcification. Other studies have found that circulatory SP-D is correlated with increased risk of both total and cardiovascular disease mortality. Both in vitro, in vivo , and clinical studies examining the relationship between SP-D and CVDs will be discussed in this review., (Copyright © 2019 Colmorten, Nexoe and Sorensen.)
- Published
- 2019
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30. Reduced CTL motility and activity in avascular tumor areas.
- Author
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Manaster Y, Shipony Z, Hutzler A, Kolesnikov M, Avivi C, Shalmon B, Barshack I, Besser MJ, Feferman T, and Shakhar G
- Subjects
- Animals, Antigens, Neoplasm immunology, Cell Movement, Cytotoxicity, Immunologic, Humans, Melanoma blood supply, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Neoplasms, Experimental, Neovascularization, Pathologic, Oxidative Phosphorylation, Perforin metabolism, Skin Neoplasms blood supply, Blood Vessels immunology, Lymphocytes, Tumor-Infiltrating immunology, Melanoma immunology, Skin Neoplasms immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Patchy infiltration of tumors by cytotoxic T cells (CTLs) predicts poorer prognosis for cancer patients. The factors limiting intratumoral CTL dissemination, though, are poorly understood. To study CTL dissemination in tumors, we histologically examined human melanoma samples and used mice to image B16-OVA tumors infiltrated by OT-I CTLs using intravital two-photon microscopy. In patients, most CTLs concentrated around peripheral blood vessels, especially in poorly infiltrated tumors. In mice, OT-I CTLs had to cluster around tumor cells to efficiently kill them in a contact-and perforin-dependent manner and cytotoxicity was strictly antigen-specific. OT-I CTLs as well as non-specific CTLs concentrated around peripheral vessels, and cleared the tumor cells around them. This was also the case when CTLs were injected directly into the tumors. CTLs crawled rapidly only in areas within 50 µm of flowing blood vessels and transient occlusion of vessels immediately, though reversibly, stopped their migration. In vitro, oxygen depletion and blockade of oxidative phosphorylation also reduced CTL motility. Taken together, these results suggest that hypoxia limits CTL migration away from blood vessels, providing immune-privileged niches for tumor cells to survive. Normalizing intratumoral vasculature may thus synergize with tumor immunotherapy.
- Published
- 2019
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31. A Neutrophil Timer Coordinates Immune Defense and Vascular Protection.
- Author
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Adrover JM, Del Fresno C, Crainiciuc G, Cuartero MI, Casanova-Acebes M, Weiss LA, Huerga-Encabo H, Silvestre-Roig C, Rossaint J, Cossío I, Lechuga-Vieco AV, García-Prieto J, Gómez-Parrizas M, Quintana JA, Ballesteros I, Martin-Salamanca S, Aroca-Crevillen A, Chong SZ, Evrard M, Balabanian K, López J, Bidzhekov K, Bachelerie F, Abad-Santos F, Muñoz-Calleja C, Zarbock A, Soehnlein O, Weber C, Ng LG, Lopez-Rodriguez C, Sancho D, Moro MA, Ibáñez B, and Hidalgo A
- Subjects
- Animals, Blood Vessels metabolism, Candida albicans immunology, Candida albicans physiology, Cells, Cultured, Cellular Senescence immunology, Chemokine CXCL2 immunology, Chemokine CXCL2 metabolism, Host-Pathogen Interactions immunology, Humans, Inflammation immunology, Inflammation metabolism, Male, Mice, Inbred C57BL, Mice, Knockout, Neutrophil Infiltration immunology, Neutrophils metabolism, Neutrophils microbiology, Receptors, CXCR4 immunology, Receptors, CXCR4 metabolism, Time Factors, Blood Vessels immunology, Circadian Rhythm immunology, Neutrophils immunology, Phagocytosis immunology
- Abstract
Neutrophils eliminate pathogens efficiently but can inflict severe damage to the host if they over-activate within blood vessels. It is unclear how immunity solves the dilemma of mounting an efficient anti-microbial defense while preserving vascular health. Here, we identify a neutrophil-intrinsic program that enabled both. The gene Bmal1 regulated expression of the chemokine CXCL2 to induce chemokine receptor CXCR2-dependent diurnal changes in the transcriptional and migratory properties of circulating neutrophils. These diurnal alterations, referred to as neutrophil aging, were antagonized by CXCR4 (C-X-C chemokine receptor type 4) and regulated the outer topology of neutrophils to favor homeostatic egress from blood vessels at night, resulting in boosted anti-microbial activity in tissues. Mice engineered for constitutive neutrophil aging became resistant to infection, but the persistence of intravascular aged neutrophils predisposed them to thrombo-inflammation and death. Thus, diurnal compartmentalization of neutrophils, driven by an internal timer, coordinates immune defense and vascular protection., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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32. Autoimmune Disease-Associated Hypertension.
- Author
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Wolf VL and Ryan MJ
- Subjects
- Blood Vessels immunology, Blood Vessels physiopathology, Humans, Inflammation physiopathology, Kidney blood supply, Kidney physiopathology, Autoimmune Diseases complications, Autoimmune Diseases immunology, Hemodynamics immunology, Hypertension etiology, Hypertension immunology, Hypertension physiopathology
- Abstract
Purpose of Review: To highlight important new findings on the topic of autoimmune disease-associated hypertension., Recent Findings: Autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis are associated with an increased risk for hypertension and cardiovascular disease. A complex interaction among genetic, environmental, hormonal, and metabolic factors contribute to autoimmune disease susceptibility while promoting chronic inflammation that can lead to alterations in blood pressure. Recent studies emphasize an important mechanistic role for autoantibodies in autoimmune disease-associated hypertension. Moving forward, understanding how sex hormones, neutrophils, and mitochondrial dysfunction contribute to hypertension in autoimmune disease will be important. This review examines the prevalent hypertension in autoimmune disease with a focus on the impact of immune system dysfunction on vascular dysfunction and renal hemodynamics as primary mediators with oxidative stress as a main contributor.
- Published
- 2019
- Full Text
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33. Neutrophil Mechanosignaling Promotes Integrin Engagement With Endothelial Cells and Motility Within Inflamed Vessels.
- Author
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Morikis VA and Simon SI
- Subjects
- Adult, Blood Vessels pathology, Endothelial Cells pathology, Female, Humans, Inflammation immunology, Inflammation pathology, Male, Neutrophils pathology, Renal Insufficiency, Chronic pathology, Blood Vessels immunology, Cell Movement immunology, Endothelial Cells immunology, Integrins immunology, Mechanotransduction, Cellular immunology, Neutrophils immunology, Renal Insufficiency, Chronic immunology
- Abstract
Neutrophils are the most motile of mammalian cells, a feature that enables them to protect the host against the rapid spread of pathogens from tissue into the circulatory system. A critical process is the recruitment of neutrophils to inflamed endothelium within post-capillary venules. This occurs through cooperation between at least four families of adhesion molecules and G-protein coupled signaling receptors. These adhesion molecules convert the drag force induced by blood flow acting on the cell surface into bond tension that resists detachment. A common feature of selectin-glycoprotein tethering and integrin-ICAM bond formation is the mechanics by which force acting on these specific receptor-ligand pairs influences their longevity, strength, and topographic organization on the plasma membrane. Another distinctly mechanical aspect of neutrophil guidance is the capacity of adhesive bonds to convert external mechanical force into internal biochemical signals through the transmission of force from the outside-in at focal sites of adhesive traction on inflamed endothelium. Within this region of the plasma membrane, we denote the inflammatory synapse, Ca
2+ release, and intracellular signaling provide directional cues that guide actin assembly and myosin driven motive force. This review provides an overview of how bond formation and outside-in signaling controls neutrophil recruitment and migration relative to the hydrodynamic shear force of blood flow.- Published
- 2018
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34. Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles.
- Author
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Choi HW, Suwanpradid J, Kim IH, Staats HF, Haniffa M, MacLeod AS, and Abraham SN
- Subjects
- ATPases Associated with Diverse Cellular Activities immunology, Animals, Blood Vessels immunology, Endosomal Sorting Complexes Required for Transport immunology, Female, Humans, Lectins, C-Type immunology, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Primary Cell Culture, Allergens immunology, Anaphylaxis immunology, Cell-Derived Microparticles immunology, Dendritic Cells immunology, Mast Cells immunology, Skin immunology
- Abstract
Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive circulating allergens remains a conundrum. Here, we describe the existence of a CD301b
+ perivascular dendritic cell (DC) subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involves the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer microvesicles (MVs) generated by vacuolar protein sorting 4 (VPS4). Antigen sharing by DCs is not limited to MCs, as neighboring DCs also acquire antigen-bearing MVs. This capacity of DCs to distribute antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2018
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35. CD49b defines functionally mature Treg cells that survey skin and vascular tissues.
- Author
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Fan X, Moltedo B, Mendoza A, Davydov AN, Faire MB, Mazutis L, Sharma R, Pe'er D, Chudakov DM, and Rudensky AY
- Subjects
- Animals, Integrin alpha2 genetics, Lymph Nodes blood supply, Lymph Nodes cytology, Lymph Nodes immunology, Mice, Mice, Transgenic, Skin blood supply, Skin cytology, T-Lymphocytes, Regulatory cytology, Blood Vessels immunology, Immunologic Surveillance, Integrin alpha2 immunology, Skin immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs and nonlymphoid tissues. While unique subsets of Treg cells have been described in some nonlymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. Furthermore, it is possible that Treg cells from similar tissue types share largely similar properties. We have identified a short-lived effector Treg cell subset that expresses the α
2 integrin, CD49b, and exhibits a unique tissue distribution, being abundant in peripheral blood, vasculature, skin, and skin-draining lymph nodes, but uncommon in the intestines and in viscera-draining lymph nodes. CD49b+ Treg cells, which display superior functionality revealed by in vitro and in vivo assays, appear to develop after multiple rounds of cell division and TCR-dependent activation. Accordingly, single-cell RNA-seq analysis placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues., (© 2018 Fan et al.)- Published
- 2018
- Full Text
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36. Intravascular large B-cell lymphoma: a chameleon with multiple faces and many masks.
- Author
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Ponzoni M, Campo E, and Nakamura S
- Subjects
- Animals, Blood Vessels immunology, Blood Vessels pathology, Cytogenetic Analysis, Disease Progression, Humans, Immunophenotyping, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse therapy, Neoplasm Staging, Prognosis, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Intravascular large B-cell lymphoma (IVLBCL) is a rare, clinically aggressive lymphoma entity characterized by an almost exclusive growth of large cells within the lumen of all sized blood vessels. The reasons for this peculiar localization of neoplastic cells are only partially understood. Clinically, in its classical variant, IVLBCL presents with many nonspecific signs and symptoms such as fever of unknown origin and involvement of the central nervous system and skin. Cases, which show disease limited to the skin, following extensive staging workup, are called cutaneous variants and show a better prognosis. In addition, a hemophagocytic variant associated with hemophagocytic syndrome and often with hepatosplenic involvement and cytopenia has been described. The classical and hemophagocytic variants are present mainly in western or Asian countries, respectively, although exceptions have been increasingly reported in both geographical areas. The cutaneous variant is mostly observed in western countries. Staging of IVLBCL is difficult and still not satisfactory. The often poor prognosis of this type of lymphoma has been substantially improved by immunochemotherapy, in particular with rituximab. Despite improved outcome, a significant proportion of patients relapse, in particular those with central nervous system manifestations. This review focuses on histopathological features, pathogenetic elements, presenting symptoms, clinical variants, disease progression, prognostic factors, therapeutic management, and the outcome of IVLBCL., (© 2018 by The American Society of Hematology.)
- Published
- 2018
- Full Text
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37. Granulomatosis with polyangiitis: clinical course and outcome of 60 patients from a single center in South India.
- Author
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Shobha V, Fathima S, and Prakash R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Blood Vessels drug effects, Blood Vessels immunology, Cyclophosphamide therapeutic use, Delayed Diagnosis, Female, Granulomatosis with Polyangiitis diagnosis, Granulomatosis with Polyangiitis drug therapy, Granulomatosis with Polyangiitis immunology, Humans, Hypertension diagnosis, Hypertension drug therapy, Hypertension immunology, Immunoglobulins, Intravenous therapeutic use, India, Kidney drug effects, Kidney immunology, Lung drug effects, Lung immunology, Male, Middle Aged, Nervous System drug effects, Nervous System immunology, Prednisolone therapeutic use, Recurrence, Retrospective Studies, Severity of Illness Index, Survival Analysis, Treatment Outcome, Blood Vessels pathology, Granulomatosis with Polyangiitis pathology, Hypertension pathology, Kidney pathology, Lung pathology, Nervous System pathology
- Abstract
Granulomatosis with polyangiitis (GPA) previously known as Wegener's granulomatosis is one of the forms of idiopathic systemic vasculitis. There is very scanty data available on GPA in Asian and Indian population. We studied data of 60 patients from southern India, diagnosed with GPA to describe the physical characteristics, the treatment, and outcome. Patients who fulfilled any two of the four criteria proposed by the American College of Rheumatology, and those with clinical features of GPA with ANCA positivity and histopathological confirmation, were included in the study. Disease activity and damage were assessed by Birmingham Vasculitis Activity Score v. 3 (BVAS v. 3) and Vasculitis Damage Index (VDI), respectively. Relapses were defined as recurrence of GPA of sufficient severity to require treatment or increase in the dose of treatment on a patient who was previously stable. Out of 60 patients, initial BVAS evaluation showed that 57 (95%) patients had severe disease and 3 (5%) patients had limited disease where median BVAS was 21.5 (range 17-44). Follow-up BVAS evaluation for severe disease showed that 13 (22.8%) patients continued with severe disease of which 9 patients did not survive, 24 (42.3%) had remission, 11 (19.2%) had persistent disease, and 9 (15.7%) were lost to follow-up. The mean VDI score was 2.5 ± 2. Renal involvement was established in 42 (70%) patients. Upper and lower respiratory involvement was seen in 38 (63%) patients. Nervous system involvement was noted in the 15 (25%) patients. Articular manifestations were seen in 16 (27%) patients. Diverse clinical manifestation delay early diagnosis and treatment of this potentially treatable vasculitis. Focused approach could expedite early diagnosis and can reduce the mortality.
- Published
- 2018
- Full Text
- View/download PDF
38. Tissue-specific immunopathology during malaria infection.
- Author
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Coban C, Lee MSJ, and Ishii KJ
- Subjects
- Animals, Blood Vessels immunology, Blood Vessels parasitology, Blood Vessels pathology, Bone and Bones immunology, Bone and Bones parasitology, Bone and Bones pathology, Brain immunology, Brain parasitology, Brain pathology, Digestive System immunology, Digestive System parasitology, Digestive System pathology, Erythrocytes immunology, Erythrocytes parasitology, Erythrocytes pathology, Host-Parasite Interactions immunology, Humans, Lymphatic System immunology, Lymphatic System parasitology, Lymphatic System pathology, Malaria parasitology, Malaria, Cerebral immunology, Malaria, Cerebral parasitology, Malaria, Cerebral pathology, Models, Immunological, Organ Specificity, Plasmodium immunology, Plasmodium pathogenicity, Retina immunology, Retina parasitology, Retina pathology, Malaria immunology, Malaria pathology
- Abstract
Systemic inflammation mediated by Plasmodium parasites is central to malaria disease and its complications. Plasmodium parasites reside in erythrocytes and can theoretically reach all host tissues via the circulation. However, actual interactions between parasitized erythrocytes and host tissues, along with the consequent damage and pathological changes, are limited locally to specific tissue sites. Such tissue specificity of the parasite can alter the outcome of malaria disease, determining whether acute or chronic complications occur. Here, we give an overview of the recent progress that has been made in understanding tissue-specific immunopathology during Plasmodium infection. As knowledge on tissue-specific host-parasite interactions accumulates, better treatment modalities and targets may emerge for intervention in malaria disease.
- Published
- 2018
- Full Text
- View/download PDF
39. Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America.
- Author
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Abreu Velez AM, Yi H, Warfvinge G, and Howard MS
- Subjects
- Armadillo Domain Proteins immunology, Atherosclerosis diagnostic imaging, Autoantibodies blood, Blood Vessels metabolism, Blood Vessels pathology, Brain blood supply, Carotid Arteries diagnostic imaging, Case-Control Studies, Cell Adhesion Molecules immunology, Colombia epidemiology, Coronary Vessels, Desmoplakins immunology, Female, Humans, Intercellular Junctions metabolism, Intervertebral Disc blood supply, Intracellular Signaling Peptides and Proteins immunology, Kidney blood supply, Male, Meninges blood supply, Phosphoproteins immunology, Plakophilins immunology, Skin blood supply, Ultrasonography, Autoantibodies immunology, Autoantibodies metabolism, Autoantigens immunology, Blood Vessels immunology, Endemic Diseases, Intercellular Junctions immunology, Pemphigus epidemiology, Pemphigus immunology
- Abstract
Background: We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF)., Methods: Here we aimed to investigate disease autoreactivity to vessels in all body organs/systems. We compared 57 patients and 57 controls from the endemic area, matched by demographics, age, sex, and work activity. We performed immunofluorescence, immunohistochemistry, confocal microscopy, immunoblotting, indirect immune electron microscopy studies, and autometallographic studies. We performed ultrasonography on large patient arteries, investigating for vascular anomalies. In addition, we reviewed autopsies on seven patients who died affected by El Bagre-EPF. We immunoadsorbed any positive vessel immunofluorescence with desmoglein (Dsg1), investigating for new autoantigens., Results: Overall, 57/57 patients affected by El Bagre-EPF displayed autoantibodies to vessels in all the organs/systems of the body via all methods (P < 0.01). The autoreactivity was polyclonal, and the patient's antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, ARVCF, and MYZAP (all from Progen Biotechnik, Germany; P < 0.01; all present at cell junctions). Immunoadsorption with Dsg1 on positive vessel immunofluorescence showed that the immune response against the vessels was directed against non-Dsg1 antigen(s). Autometallographic studies showed deposits of metals and metalloids in vessel cell junctions and in erythrocytes of 85% of patients (P < 0.01)., Conclusions: Immune response to these vascular antigens is likely altering endothelial cells and vessel shapes, thus disturbing hemodynamic flow. The flow alterations likely lead to inflammation and may play a role in the atherogenesis often seen in these patients., (© 2017 The International Society of Dermatology.)
- Published
- 2018
- Full Text
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40. The immunoinhibitory PD-1/PD-L1 pathway in inflammatory blood vessel disease.
- Author
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Weyand CM, Berry GJ, and Goronzy JJ
- Subjects
- Blood Vessels metabolism, Blood Vessels pathology, Coronary Artery Disease metabolism, Coronary Artery Disease pathology, Giant Cell Arteritis metabolism, Giant Cell Arteritis pathology, Humans, Inflammation metabolism, Inflammation pathology, T-Lymphocytes metabolism, T-Lymphocytes pathology, B7-H1 Antigen antagonists & inhibitors, Blood Vessels immunology, Coronary Artery Disease immunology, Giant Cell Arteritis immunology, Inflammation immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors, T-Lymphocytes immunology
- Abstract
Because of their vital function, the wall structures of medium and large arteries are immunoprivileged and protected from inflammatory attack. That vascular immunoprivilege is broken in atherosclerosis and in vasculitis, when wall-invading T cells and macrophages (Mϕ) promote tissue injury and maladaptive repair. Historically, tissue-residing T cells were studied for their antigen specificity, but recent progress has refocused attention to antigen-nonspecific regulation, which determines tissue access, persistence, and functional differentiation of T cells. The coinhibitory receptor PD-1, expressed on T cells, delivers negative signals when engaged by its ligand PD-L1, expressed on dendritic cells, Mϕ, and endothelial cells to attenuate T cell activation, effector functions, and survival. Through mitigating signals, the PD-1 immune checkpoint maintains tissue tolerance. In line with this concept, dendritic cells and Mϕs from patients with the vasculitic syndrome giant cell arteritis (GCA) are PD-L1
lo ; including vessel-wall-embedded DCs that guard the vascular immunoprivilege. GCA infiltrates in the arterial walls are filled with PD-1+ T cells that secrete IFN-γ, IL-17, and IL-21; drive inflammation-associated angiogenesis; and facilitate intimal hyperplasia. Conversely, chronic tissue inflammation in the atherosclerotic plaque is associated with an overreactive PD-1 checkpoint. Plaque-residing Mϕs are PD-L1hi , a defect induced by their addiction to glucose and glycolytic breakdown. PD-L1hi Mϕs render patients with coronary artery disease immunocompromised and suppress antiviral immunity, including protective anti-varicella zoster virus T cells. Thus, immunoinhibitory signals affect several domains of vascular inflammation; failing PD-L1 in vasculitis enables unopposed immunostimulation and opens the flood gates for polyfunctional inflammatory T cells, and excess PD-L1 in the atherosclerotic plaque disables tissue-protective T cell immunity., (©2017 Society for Leukocyte Biology.)- Published
- 2018
- Full Text
- View/download PDF
41. The perivascular origin of pathological fibroblasts.
- Author
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Di Carlo SE and Peduto L
- Subjects
- Animals, Blood Vessels immunology, Blood Vessels metabolism, Blood Vessels pathology, Fibroblasts pathology, Fibrosis, Humans, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells pathology, Collagen immunology, Collagen metabolism, Fibroblasts immunology, Fibroblasts metabolism, Mesenchymal Stem Cells immunology
- Abstract
The ability to repair tissues is essential for the survival of organisms. In chronic settings, the failure of the repair process to terminate results in overproduction of collagen, a pathology known as fibrosis, which compromises organ recovery and impairs function. The origin of the collagen-overproducing cell has been debated for years. Here we review recent insights gained from the use of lineage tracing approaches in several organs. The resulting evidence points toward specific subsets of tissue-resident mesenchymal cells, mainly localized in a perivascular position, as the major source for collagen-producing cells after injury. We discuss these findings in view of the functional heterogeneity of mesenchymal cells of the perivascular niche, which have essential vascular, immune, and regenerative functions that need to be preserved for efficient repair.
- Published
- 2018
- Full Text
- View/download PDF
42. Reprogramming Tumor Blood Vessels for Enhancing Immunotherapy.
- Author
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Schmittnaegel M and De Palma M
- Subjects
- Angiopoietin-2 antagonists & inhibitors, Angiopoietin-2 genetics, Angiopoietin-2 immunology, Blood Vessels growth & development, Blood Vessels pathology, Cellular Reprogramming genetics, Cellular Reprogramming immunology, Humans, Immunosuppression Therapy methods, Immunotherapy methods, Neoplasms therapy, T-Lymphocytes pathology, Blood Vessels immunology, Neoplasms immunology, T-Lymphocytes immunology, Tumor Microenvironment immunology
- Abstract
Angiogenic blood vessels contribute to generating an immunosuppressive tumor microenvironment, in part by limiting the extravasation of T cells. Functional reprogramming of angiogenic blood vessels, for example through angiopoietin-2 blockade, may improve T cell trafficking in tumors and the efficacy of immune checkpoint blockade (ICB) and other cancer immunotherapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
43. Tumor-associated macrophages are strongly related to vascular invasion, non-luminal subtypes, and interval breast cancer.
- Author
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Klingen TA, Chen Y, Aas H, Wik E, and Akslen LA
- Subjects
- Aged, Blood Vessels immunology, Breast Neoplasms immunology, Breast Neoplasms mortality, Breast Neoplasms therapy, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Lymphatic Metastasis, Lymphatic Vessels immunology, Macrophages immunology, Middle Aged, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Norway, Phenotype, Platelet Endothelial Cell Adhesion Molecule-1 analysis, Proportional Hazards Models, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Up-Regulation, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, Biomarkers, Tumor analysis, Blood Vessels pathology, Breast Neoplasms pathology, Lymphatic Vessels pathology, Macrophages pathology, Receptors, Cell Surface analysis
- Abstract
Tumor-associated macrophages (TAM) resemble M2 macrophages, promote tumor invasion and show strong expression of CD163 in breast cancer. We here investigated the association between CD163-positive macrophages and vascular invasion, molecular subgroups, mode of detection, and patient outcome. We performed a population-based, retrospective study of invasive breast cancer from the Norwegian Breast Cancer Screening Programme in Vestfold County (2004-2009), including 200 screen-detected and 82 interval cancers. Immunohistochemically CD163-positive macrophages were counted in the most active areas (hotspots) and dichotomized as high (upper quartile) and low counts. Lymphatic vessel involvement (LVI) and blood vessel invasion (BVI) were recorded separately based on immunohistochemical staining (D2-40 and CD31 antibodies). High levels of CD163-positive macrophages were associated with BVI and lymphatic involvement as well as interval cancer detection when compared to screening-detected tumors. In addition, the presence of high CD163+ TAM levels was more often observed in HER2-positive, basal-like and Triple-negative breast cancers and was associated with several features of aggressive tumors. In survival analyses, cases with combined high CD163 counts and BVI showed a significantly reduced recurrence-free survival (RFS) and disease-specific survival (DSS) (P < .001 for both) compared with all other cases. The presence of CD163-positive, tumor-associated macrophages is strongly related to aggressive features of breast cancer such as vessel invasion, detection between screening intervals, non-luminal molecular subgroups and reduced survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
44. Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation.
- Author
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Xu Y, Wang Y, Yan S, Yang Q, Zhou Y, Zeng X, Liu Z, An X, Toque HA, Dong Z, Jiang X, Fulton DJ, Weintraub NL, Li Q, Bagi Z, Hong M, Boison D, Wu C, and Huo Y
- Subjects
- Adenosine Kinase genetics, Adenosylhomocysteinase metabolism, Animals, Atherosclerosis genetics, Cerebral Cortex blood supply, Epigenesis, Genetic genetics, Gene Knockdown Techniques, Inflammation genetics, Inflammation immunology, Mice, Mice, Knockout, ApoE, Reperfusion Injury genetics, Reperfusion Injury immunology, Adenosine immunology, Adenosine Kinase immunology, Atherosclerosis immunology, Blood Vessels immunology, Endothelial Cells immunology, Epigenesis, Genetic immunology, Gene Expression Regulation immunology
- Abstract
The molecular mechanisms underlying vascular inflammation and associated inflammatory vascular diseases are not well defined. Here we show that endothelial intracellular adenosine and its key regulator adenosine kinase (ADK) play important roles in vascular inflammation. Pro-inflammatory stimuli lead to endothelial inflammation by increasing endothelial ADK expression, reducing the level of intracellular adenosine in endothelial cells, and activating the transmethylation pathway through increasing the association of ADK with S-adenosylhomocysteine (SAH) hydrolase (SAHH). Increasing intracellular adenosine by genetic ADK knockdown or exogenous adenosine reduces activation of the transmethylation pathway and attenuates the endothelial inflammatory response. In addition, loss of endothelial ADK in mice leads to reduced atherosclerosis and affords protection against ischemia/reperfusion injury of the cerebral cortex. Taken together, these results demonstrate that intracellular adenosine, which is controlled by the key molecular regulator ADK, influences endothelial inflammation and vascular inflammatory diseases.The molecular mechanisms underlying vascular inflammation are unclear. Here the authors show that pro-inflammatory stimuli lead to endothelial inflammation by increasing adenosine kinase expression, and that its knockdown in endothelial cells inhibits atherosclerosis and cerebral ischemic injury in mice.
- Published
- 2017
- Full Text
- View/download PDF
45. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function.
- Author
-
Terao J
- Subjects
- Absorption, Physiological, Animals, Antioxidants adverse effects, Antioxidants metabolism, Antioxidants therapeutic use, Blood Vessels immunology, Blood Vessels metabolism, Blood Vessels physiology, Blood Vessels physiopathology, Digestion, Endothelium, Vascular immunology, Endothelium, Vascular metabolism, Endothelium, Vascular physiopathology, Flavonoids adverse effects, Flavonoids blood, Flavonoids metabolism, Gastrointestinal Microbiome, Glycosylation, Humans, Hydrolysis, Macrophages immunology, Macrophages metabolism, Oxidative Stress, Prenylation, Quercetin adverse effects, Quercetin metabolism, Quercetin therapeutic use, Vascular Diseases immunology, Vascular Diseases metabolism, Vascular Diseases physiopathology, Diet, Healthy, Dietary Supplements adverse effects, Endothelium, Vascular physiology, Flavonoids therapeutic use, Intestinal Absorption, Quercetin analogs & derivatives, Vascular Diseases prevention & control
- Abstract
Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
46. How neutrophils resist shear stress at blood vessel walls: molecular mechanisms, subcellular structures, and cell-cell interactions.
- Author
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Begandt D, Thome S, Sperandio M, and Walzog B
- Subjects
- CD18 Antigens immunology, Leukocyte Rolling immunology, Blood Platelets immunology, Blood Vessels immunology, Cell Communication immunology, Neutrophils immunology, Shear Strength, Stress, Physiological immunology
- Abstract
Neutrophils are the first cells arriving at sites of tissue injury or infection to combat invading pathogens. Successful neutrophil recruitment to sites of inflammation highly depends on specific molecular mechanisms, fine-tuning the received information into signaling pathways and converting them into well-described recruitment steps. This review highlights the impact of vascular flow conditions on neutrophil recruitment and the multitude of mechanisms developed to enable this sophisticated process under wall shear stress conditions. The recruitment process underlies a complex interplay between adhesion and signaling molecules, as well as chemokines, in which neutrophils developed specific mechanisms to travel to sites of lesion in low and high shear stress conditions. Rolling, as the first step in the recruitment process, highly depends on endothelial selectins and their ligands on neutrophils, inducting of intracellular signaling and subsequently activating β
2 integrins, enabling adhesion and postadhesion events. In addition, subcellular structures, such as microvilli, tethers, and slings allow the cell to arrest, even under high wall shear stress. Thereby, microvilli that are pulled out from the cell body form tethers that develop into slings upon their detachment from the substrate. In addition to the above-described primary capture, secondary capture of neutrophils via neutrophil-neutrophil or neutrophil-platelet interaction promotes the process of neutrophil recruitment to sites of lesion. Thus, precise mechanisms based on a complex molecular interplay, subcellular structures, and cell-cell interactions turn the delicate process of neutrophil trafficking during flow into a robust response allowing effective neutrophil accumulation at sites of injury., (© Society for Leukocyte Biology.)- Published
- 2017
- Full Text
- View/download PDF
47. Macrophage deficiency of miR-21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis.
- Author
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Canfrán-Duque A, Rotllan N, Zhang X, Fernández-Fuertes M, Ramírez-Hidalgo C, Araldi E, Daimiel L, Busto R, Fernández-Hernando C, and Suárez Y
- Subjects
- ATP Binding Cassette Transporter, Subfamily G, Member 1 genetics, ATP Binding Cassette Transporter, Subfamily G, Member 1 immunology, Animals, Atherosclerosis genetics, Atherosclerosis immunology, Atherosclerosis pathology, Blood Vessels immunology, Female, Humans, MAP Kinase Kinase 3 genetics, MAP Kinase Kinase 3 immunology, Macrophages cytology, Male, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs genetics, Necrosis genetics, Necrosis immunology, Necrosis pathology, Necrosis physiopathology, Apoptosis, Atherosclerosis physiopathology, Macrophages immunology, MicroRNAs immunology
- Abstract
Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. Here, we define the contribution of miR-21 in hematopoietic cells during atherogenesis. Interestingly, we found that miR-21 is the most abundant miRNA in macrophages and its absence results in accelerated atherosclerosis, plaque necrosis, and vascular inflammation. miR-21 expression influences foam cell formation, sensitivity to ER-stress-induced apoptosis, and phagocytic clearance capacity. Mechanistically, we discovered that the absence of miR-21 in macrophages increases the expression of the miR-21 target gene, MKK3, promoting the induction of p38-CHOP and JNK signaling. Both pathways enhance macrophage apoptosis and promote the post-translational degradation of ABCG1, a transporter that regulates cholesterol efflux in macrophages. Altogether, these findings reveal a major role for hematopoietic miR-21 in atherogenesis., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2017
- Full Text
- View/download PDF
48. The Upregulation of Integrin α D β 2 (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis.
- Author
-
Aziz MH, Cui K, Das M, Brown KE, Ardell CL, Febbraio M, Pluskota E, Han J, Wu H, Ballantyne CM, Smith JD, Cathcart MK, and Yakubenko VP
- Subjects
- Animals, Aorta immunology, Aorta pathology, Apolipoproteins E deficiency, Atherosclerosis etiology, Atherosclerosis pathology, Blood Vessels immunology, CD11 Antigens immunology, CD18 Antigens immunology, Diet, Western, Humans, Inflammation pathology, Inflammation Mediators metabolism, Integrin alpha Chains deficiency, Integrin alpha Chains immunology, Macrophages metabolism, Macrophages pathology, Mice, Mice, Knockout, Peritonitis immunology, Peritonitis pathology, Transcriptional Activation, Up-Regulation, Atherosclerosis immunology, Blood Vessels pathology, CD11 Antigens genetics, CD18 Antigens genetics, Integrin alpha Chains genetics, Macrophages immunology
- Abstract
Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin α
D β2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion. In this study, we have investigated how inflammation-mediated CD11d upregulation contributes to macrophage retention at inflammatory sites during atherogenesis. Atherosclerosis was evaluated in CD11d-/- /ApoE-/- mice after 16 wk on a Western diet. CD11d deficiency led to a marked reduction in lipid deposition in aortas and isolated macrophages. Macrophage numbers in aortic sinuses of CD11d-/- mice were reduced without affecting their apoptosis and proliferation. Adoptive transfer of fluorescently labeled wild-type and CD11d-/- monocytes into ApoE-/- mice demonstrated similar recruitment from circulation, but reduced accumulation of CD11d-/- macrophages within the aortas. Furthermore, CD11d expression was significantly upregulated on macrophages in atherosclerotic lesions and M1 macrophages in vitro. Interestingly, expression of the related ligand-sharing integrin CD11b was not altered. This difference defines their distinct roles in the regulation of macrophage migration. CD11d-deficient M1 macrophages demonstrated improved migration in a three-dimensional fibrin matrix and during resolution of peritoneal inflammation, whereas migration of CD11b-/- M1 macrophages was not affected. These results prove the contribution of high densities of CD11d to macrophage arrest during atherogenesis. Because high expression of CD11d was detected in several inflammation-dependent diseases, we suggest that CD11d/CD18 upregulation on proinflammatory macrophages may represent a common mechanism for macrophage retention at inflammatory sites, thereby promoting chronic inflammation and disease development., (Copyright © 2017 by The American Association of Immunologists, Inc.)- Published
- 2017
- Full Text
- View/download PDF
49. Study of fluid dynamics reveals direct communications between lymphatic vessels and venous blood vessels at lymph nodes of mice.
- Author
-
Takeda K, Mori S, and Kodama T
- Subjects
- Animals, Blood Vessels pathology, Lymph Nodes pathology, Lymphatic Metastasis pathology, Lymphatic Vessels pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Inbred Strains, Tumor Cells, Cultured, Blood Vessels immunology, Hydrodynamics, Lymph Nodes immunology, Lymphatic Metastasis immunology, Lymphatic Vessels immunology
- Abstract
Cancer cells metastasize to lymph nodes, with distant metastasis resulting in poor prognosis. The role of lymph node metastasis (LNM) in the spread of cancer to distant organs remain incompletely characterized. The visualization of flow dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 10mm in diameter, has revealed that lymph nodes have the potential to be a direct source of systemic metastasis. However, it is not known whether these fluid dynamics characteristics are universal phenomena present in other strains of laboratory mice. Here we show that the fluid dynamics observed in MXH10/Mo-lpr/lpr mice are the same as those observed in C57BL/6J, BALB/cAJcl and NOD/ShiJic-scidJcl mice. Furthermore, when fluorescent solution was injected into a tumor-bearing lymph node, the flow dynamics observed in the efferent lymphatic vessels and thoracoepigastric vein depended on the type of tumor cell. Our results indicate that fluid dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice are generalized phenomena seen in conventional laboratory mice. We anticipate our results can facilitate studies of the progression of lymphatic metastasis to hematogenous metastasis via lymph nodes and the early diagnosis and treatment of LNM., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
50. Tumour ischaemia by interferon-γ resembles physiological blood vessel regression.
- Author
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Kammertoens T, Friese C, Arina A, Idel C, Briesemeister D, Rothe M, Ivanov A, Szymborska A, Patone G, Kunz S, Sommermeyer D, Engels B, Leisegang M, Textor A, Fehling HJ, Fruttiger M, Lohoff M, Herrmann A, Yu H, Weichselbaum R, Uckert W, Hübner N, Gerhardt H, Beule D, Schreiber H, and Blankenstein T
- Subjects
- Animals, Blood Vessels immunology, Blood Vessels metabolism, Cell Line, Tumor, Endothelial Cells immunology, Endothelial Cells metabolism, Female, Interferon-gamma biosynthesis, Intravital Microscopy, Ischemia metabolism, Ischemia pathology, Male, Mice, Necrosis, Neoplasms metabolism, Neoplasms pathology, Receptors, Interferon metabolism, Stromal Cells immunology, Stromal Cells metabolism, Substrate Specificity, Wound Healing, Interferon gamma Receptor, Blood Vessels growth & development, Cell Hypoxia immunology, Interferon-gamma immunology, Ischemia immunology, Neoplasms blood supply, Neoplasms immunology, Vascular Remodeling
- Abstract
The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models. Although IFNγ can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection of large, established tumours. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ-GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types. Responsiveness to IFNγ by myeloid cells and other haematopoietic cells, including T cells or fibroblasts, was not sufficient for IFNγ-induced tumour regression, whereas responsiveness of endothelial cells to IFNγ was necessary and sufficient. Intravital microscopy revealed IFNγ-induced regression of the tumour vasculature, resulting in arrest of blood flow and subsequent collapse of tumours, similar to non-haemorrhagic necrosis in ischaemia and unlike haemorrhagic necrosis induced by tumour necrosis factor. The early events of IFNγ-induced tumour ischaemia resemble non-apoptotic blood vessel regression during development, wound healing or IFNγ-mediated, pregnancy-induced remodelling of uterine arteries. A better mechanistic understanding of how solid tumours are rejected may aid the design of more effective protocols for adoptive T-cell therapy.
- Published
- 2017
- Full Text
- View/download PDF
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