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Abstract Cell–cell fusion is a vital biological process where the membranes of two or more cells merge to form a syncytium. This phenomenon is critical in various physiological and pathological contexts, including embryonic development, tissue repair, immune responses, and the progression of several diseases. Osteoclasts, which are cells from the monocyte/macrophage lineage responsible for bone resorption, have enhanced functionality due to cell fusion. Additionally, other multinucleated giant cells (MGCs) also arise from the fusion of monocytes and macrophages, typically during chronic inflammation and reactions to foreign materials such as prostheses or medical devices. Foreign body giant cells (FBGCs) and Langhans giant cells (LGCs) emerge only under pathological conditions and are involved in phagocytosis, antigen presentation, and the secretion of inflammatory mediators. This review provides a comprehensive overview of the mechanisms underlying the formation of multinucleated cells, with a particular emphasis on macrophages and osteoclasts. Elucidating the intracellular structures, signaling cascades, and fusion-mediating proteins involved in cell–cell fusion enhances our understanding of this fundamental biological process and helps identify potential therapeutic targets for disorders mediated by cell fusion.

Abstract Previous studies have reported that senolytic drugs can reverse obesity-mediated accumulation of senescent cells in the ovary and protect against cisplatin-induced ovarian injury by removing senescent cells. Early intervention with ABT-263 has been shown to mitigate ovarian aging. However, it remains unknown whether treatment with ABT-263 could rejuvenate the aged ovary in reproductively old females. Therefore, the current study was aimed to investigate whether advanced age intervention with ABT-263 could ameliorate age-related decline in ovarian function. Fourteen 16-month-old mice with a C57/BL6 background were treated with ABT-263 (N = 7) or vehicle (N = 7) for two weeks. Mice were initially treated with ABT-263 (60 mg/kg/d) or vehicle for 7 consecutive days. After a 7-day break, the treatment was repeated for another 7 consecutive days. Six 2-month-old mice with C57BL/6 were used as a young control. The hormonal levels, estrus cycles, ovarian reserve, ovarian cell proliferation and apoptosis, ovarian fibrosis, and steroidogenic gene expression of ovarian stromal cells were evaluated. ABT-263 treatment did not rescue abnormal estrus cycles and sex hormonal levels, or inhibit the formation of multinucleated giant cells and ovarian stromal cell apoptosis in aged ovaries. However, it reduced ovarian fibrosis and preserved the steroidogenic gene expression of ovarian stromal cells in aged ovaries. Importantly, ABT-263 treatment further depleted ovarian follicles in aged mice. In conclusion, ABT-263 treatment accelerated the depletion of ovarian follicles in aged mice, suggesting that senolytic drugs for reproductively old female may adversely affect female fertility.

Background. Local antibacterial therapy in the treatment of osteomyelitis significantly increases the effectiveness of surgical debridement.The aim of the work. To assess in an in vivo experiment the dynamics of perifocal tissue reactions to the application of an original polyvinylpyrrolidone-based antimicrobial gel in a one-stage treatment of implant-associated infection in the hip joint in rabbits.Methods. Implant-associated infection was modeled by inserting Staphylococcus aureus-infected wires into the medullary canal of the femur of rabbits (n = 12). On the day 14, we removed the wire and performed radical surgical treatment of the suppurative focus and hip replacement. The animals were divided into two groups: experimental group – with application of the original antimicrobial gel at the stage of hip replacement (n = 6); comparison group – without gel application (n = 6). For morphological studies, animals were sacrificed on the days 10, 45 and 90 after hip replacement, changes in soft tissues and the bone marrow canal were assessed, and cell populations were counted with statistical data processing.Results. The application of the original antimicrobial gel causes statistically significant decrease in the number of neutrophils in the soft tissues surrounding the implant in the comparison group at all stages. Moreover, in the experimental group, at early stages the number of lymphocytes, plasmacytes and macrophages was statistically significantly higher; on the day 45, a statistically significantly larger number of lymphocytes was registered, and on the day 90 – a statistically significantly larger number of multinucleated and epithelioid cells.Conclusion. The experiment histologically confirmed the effectiveness of application of the original antimicrobial gel to stop infectious inflammation in soft tissues and the bone marrow canal during surgical debridement of an osteomyelitic lesion followed by hip replacement. A pronounced giant cell reaction aimed at removing the polyvinylpyrrolidone-based gel requires further research in terms of its outcomes.

Central Giant Cell Granuloma (CGCG) is a reactive, benign bony lesion primarily affecting the jaw bones of unknown etiology. Its widespread clinical manifestations can make diagnosis challenging. It is usually seen in mandible but can also involve the maxilla and hence should be considered as a differential diagnosis. Both surgical and non-surgical method can be considered but conservative surgical excision is the widely used treatment approach for management of CGCG.

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells through trophic, clearance, and cytocidal functions. During evolution, they contributed to the innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at mid-gestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac, AGM, and fetal liver-derived tissue-resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for the discovery of dendritic cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity.

Hematoma clearance is critical for mitigating intracerebral hemorrhage (ICH)-induced brain injury. Multinucleated giant cells (MGCs), a type of phagocyte, and the complement system may play a pivotal role in hematoma resolution, but whether the complement system regulates MGC formation after ICH remains unclear. The current study investigated the following: (1) the characteristics of MGC formation after ICH, (2) whether it was impacted by complement C3 deficiency in mice and (3) whether it also influenced hematoma degradation (hemosiderin formation). Young and aged male mice, young female mice and C3-deficient and -sufficient mice received a 30 μL injection of autologous whole blood into the right basal ganglia. Brain histology and immunohistochemistry were used to examine MGC formation on days 3 and 7. Hemosiderin deposition was examined by autofluorescence on day 28. Following ICH, MGCs were predominantly located in the peri-hematoma region exhibiting multiple nuclei and containing red blood cells or their metabolites. Aging was associated with a decrease in MGC formation after ICH, while sex showed no discernible effect. C3 deficiency reduced MGC formation and reduced hemosiderin formation. Peri-hematomal MGCs may play an important role in hematoma resolution. Understanding how aging and complement C3 impact MGCs may provide important insights into how to regulate hematoma resolution.

The soil saprophyte, Burkholderia pseudomallei, is the causative agent of melioidosis, a disease endemic in South East Asia and northern Australia. Exposure to B. pseudomallei by either inhalation or inoculation can lead to severe disease. B. pseudomallei rapidly shifts from an environmental organism to an aggressive intracellular pathogen capable of rapidly spreading around the body. The expression of multiple virulence factors at every stage of intracellular infection allows for rapid progression of infection. Following invasion or phagocytosis, B. pseudomallei resists host-cell killing mechanisms in the phagosome, followed by escape using the type III secretion system. Several secreted virulence factors manipulate the host cell, while bacterial cells undergo a shift in energy metabolism allowing for overwhelming intracellular replication. Polymerisation of host cell actin into “actin tails” propels B. pseudomallei to the membranes of host cells where the type VI secretion system fuses host cells into multinucleated giant cells (MNGCs) to facilitate cell-to-cell dissemination. This review describes the various mechanisms used by B. pseudomallei to survive within cells.

Surgical resection is the gold standard for an aggressive variant of central giant cell granuloma (CGCG) which causes permanent disfigurement, especially in young individuals. Therefore, the conservative line of treatment should be tried first. Jacoway and colleagues proposed that the intralesional administration of corticosteroids acts on the giant cells that have osteoclasts receptors present on their surface and thus, corticosteroids induce apoptosis, causing remission of the lesion. An 11-year girl reported non-tender bony swelling in the left mandibular region for 3 months. CBCT revealed a large lytic lesion from teeth 33 to 37 measuring about 4 cm × 4 cm approximately. A biopsy was done, which diagnosed the lesion as central giant cell granuloma. 10 mg/ml of triamcinolone acetonide intralesional injection per cm of the lesion was injected. The protocol of initially giving intralesional corticosteroid injections can be used as a first treatment option for the management of CGCG rather than going for an initial aggressive surgical approach.

Sulfated glycosaminoglycans (sGAG) show interaction with biological mediator proteins. Although collagen-based biomaterials are widely used in clinics, their combination with high-sulfated hyaluronan (sHA3) is unexplored. This study aims to functionalize a collagen-based scaffold (Mucograft®) with sHA3 via electrostatic (sHA3/PBS) or covalent binding to collagen fibrils (sHA3+EDC/NHS). Crosslinking without sHA3 was used as a control (EDC/NHS Ctrl). The properties of the sHA3-functionalized materials were characterized. In vitro growth factor and cytokine release after culturing with liquid platelet-rich fibrin was performed by means of ELISA. The cellular reaction to the biomaterials was analyzed in a subcutaneous rat model. The study revealed that covalent linking of sHA3 to collagen allowed only a marginal release of sHA3 over 28 days in contrast to electrostatically bound sHA3. sHA3+EDC/NHS scaffolds showed reduced vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-β1) and enhanced interleukin-8 (IL-8) and epithelial growth factor (EGF) release in vitro compared to the other scaffolds. Both sHA3/PBS and EDC/NHS Ctrl scaffolds showed a high proinflammatory reaction (M1: CD-68+/CCR7+) and induced multinucleated giant cell (MNGC) formation in vivo. Only sHA3+EDC/NHS scaffolds reduced the proinflammatory macrophage M1 response and did not induce MNGC formation during the 30 days. SHA3+EDC/NHS scaffolds had a stable structure in vivo and showed sufficient integration into the implantation region after 30 days, whereas EDC/NHS Ctrl scaffolds underwent marked disintegration and lost their initial structure. In summary, functionalized collagen (sHA3+EDC/NHS) modulates the inflammatory response and is a promising biomaterial as a stable scaffold for full-thickness skin regeneration in the future.

Background: The purpose of our work was determined by the accumulation of a significant amount of experimental material under the conditions of implantation of a foreign body, a mesh implant, into the region of the anterior abdominal wall in order to obtain experimental inflammation, in which foreign body giant cells (FBGCs) were constantly visualized as reactive formations. This research aimed to study the dynamics of morphological changes in FBGCs under conditions of experimental implantation of a foreign body, a mesh implant, and the possible mechanism of their formation Methods and Results: This study was carried out on male Wistar rats, in which a foreign body was implanted—a mesh endoprosthesis made of polypropylene—in the region of the anterior abdominal wall under the aponeurosis of the rectus abdominis muscles. A section of the anterior abdominal wall with the implanted endoprosthesis was excised on Days 10, 21, 30, and 60 after surgery, fixed in 10% buffered formalin solution. The obtained samples were embedded in paraffin according to standard prescriptions; histological sections with a thickness of 5-7µm were made and stained with H&E, according to the methods of Van Gieson and Mallory, and an immunohistochemical study was performed using the marker of cell proliferation (Ki-67). The revealed structural features of multinucleated cells were recorded by microphotography using a photo attachment and a Levenhuk video camera (USA). During the study, it was revealed that the amount, functional activity and morphological diversity of FBGCs gradually increased, reaching a maximum by Day 30 of the experiment. At a later date, some of them died, while the remaining part was differentiated, splitting into small multinucleated cells and mononuclear elements, morphologically identical to macrophages and fibroblasts. The formation of FBGCs continued as long as the mesh implant was in the body. Conclusion: FBGCs are reactive formations that arise in response to various endo- and exogenous irritation.

Giant cells are formed by the union of several monocytes or macrophages which undergo a defined set of intercellular interactions that ultimately results in a multinucleated cell with a single cytoplasmic compartment. Giant cells are not only pathologic, there are even physiologic giant cells such as osteoclast, megakaryocytes, and trophoblast that helps in maintaining normal repair and remodeling process in the body. There are various classifications and theories for the formation of giant cells. Some of these giant cells act as a characteristic histopathologic feature in oral lesions and aid in diagnosis. In the field of challenging diagnosis, these characteristic features can provide a clue for diagnosing some oral lesions. On this background, the article was attempted to review various types of giant cells, their formation, and giant cell lesions of the oral cavity with basic information about their clinical, radiologic, histopathological features, and treatment planning.

The lysX gene from Mycobacterium avium hominissuis (MAH) is not only involved in cationic antimicrobial resistance but also regulates metabolic activity. An MAH lysX deficient mutant was shown to exhibit a metabolic shift at the extracellular state preadapting the bacteria to the conditions inside host-cells. It further showed stronger growth in human monocytes. In the present study, the LysX activity on host–pathogen interactions were analyzed. The lysX mutant from MAH proved to be more sensitive toward host-mediated stresses such as reactive oxygen species. Further, the lysX mutant exhibited increased inflammatory response in PBMC and multinucleated giant cell (MGC) formation in human macrophages during infection studies. Coincidentally, the lysX mutant strain revealed to be more reproductive in the Galleria mellonella infection model. Together, these data demonstrate that LysX plays a role in regulating the bacillary load in host organisms and the lack of lysX gene facilitates MAH adaptation to intracellular host-habitat, thereby suggesting an essential role of LysX in the modulation of host–pathogen interaction.

Introduction: Giant Cell Tumour of Tendon Sheath (GCTTS), also known as localised nodular tenosynovitis, is a slow growing benign soft tissue tumour arising from synovium of tendon sheath, bursa or joint. Clinically, the lesions occur as skin-coloured nodules typically on the extremities. These tumours occur more frequently on the upper limbs especially hands (77%) where they form the second most common tumour following simple ganglion cyst. Aim: To describe the cytomorphologic findings in GCTTS and their histopathological features. Materials and Methods: This retrospective study was conducted at Department of Pathology, ESI Hospital, New Delhi, India, in 12 diagnosed GCTTS cases for their cytological features from January 2015 to December 2017. Fine Needle Aspiration Cytology (FNAC) was performed with a 22-gauge needle attached to a 10 mL syringe. Smears were air-dried and stained with Giemsa stain. Cytomorphology of all the selected cases were analysed and descriptive statistics were used to evaluate the cases. Results: A total of 12 cases of GCTTS were retrieved. Diagnosis of GCTTS was made by FNAC in all the cases and confirmed by histopathological examination in half of the cases. The mean age of presentation was 39 years. Of these, 8 (66.67%) were women and 4 (33.33%) were men. The lesions were found most commonly over the index finger (n=5) followed by the ring finger (n=3), thumb (n=2), middle finger (n=1) and little finger (n=1). The most frequent clinical presentation was a painless, nodular, slow growing firm swelling over the finger. FNAC revealed cellular smears with few clusters and numerous scattered stromal cells along with interspersed multinucleated giant cells. Conclusion: A definitive preoperative diagnosis of GCTTS obtained through FNAC helps in formulating appropriate treatment plan. Histopathologic examination will confirm the cytological diagnosis and can help to predict recurrence by providing information on the resection margin, any satellite nodules, variable cell types and mitotic activity.

A characteristic feature of sarcoidosis is a dysregulated immune response to persistent stimuli, often leading to the formation of non-necrotizing granulomas in various organs. Although genetic susceptibility is an essential factor in disease development, the etiology of sarcoidosis is not fully understood. Specifically, whether autoimmunity contributes to the initiation or progression of the disease is uncertain. In this study, we investigated systemic autoimmunity to vimentin in sarcoidosis. IgG antibodies to human vimentin were measured in sera from sarcoidosis patients and healthy controls. Mice immunized with recombinant murine vimentin were challenged intravenously with vimentin-coated beads to mimic pulmonary sarcoidosis. Lungs from treated mice were studied for cellular infiltration, granuloma formation, and gene expression. Immune cells in the bronchoalveolar lavage fluid were evaluated by flow cytometry. Compared to healthy controls, sarcoidosis patients had a higher frequency and levels of circulating anti-vimentin IgG. Vimentin-immunized mice developed lung granulomas following intravenous challenge with vimentin-coated beads. These sarcoidosis-like granulomas showed the presence of Langhans and foreign body multinucleated giant cells, CD4 T cells, and a heterogeneous collection of MHC II positive and arginase 1-expressing macrophages. The lungs showed upregulated pro-inflammatory gene expression, including Ifng, Il17, and Tnfa, reflecting TH1/TH17 responses typical of sarcoidosis. In addition, genes in the TH2 canonical pathway were also upregulated, congruent with increased numbers of ILC2 in the bronchoalveolar lavage. Overall, these results further validate vimentin as an autoantigen in sarcoidosis and provide evidence for an anti-vimentin immune response in disease pathogenesis. Our study also highlights the possible role of ILC2-driven TH2-like responses in the formation of lung granulomas in sarcoidosis.

Ovarian ageing stands as the major contributor towards fertility loss. As such, there is an urge for studies addressing the mechanisms that promote ovarian ageing and new strategies aiming to delay it. Recently, the presence of a unique population of multinucleated giant cells has been identified in the ovaries of reproductively aged mice. These cells have been considered hallmarks of ovarian ageing. However, up to date multinucleated giant cells have only been described in the ovaries of the mice. Therefore, the aim of the present work was to evaluate and characterize the presence of such hallmarks of ovarian ageing in the sheep and the goat. In this study, ovaries from juvenile (6 months) and mature animals (18–24 months) were used. The hematoxylin and eosin technique was performed to describe the ovarian morphology and evaluate the ovarian follicle reserve pool. Sudan black B staining and the detection of autofluorescence emission were used to identify and characterize the presence of multinucleated giant cells. Statistical analyses were performed with GraphPad Prism 9.0.0. A decrease in the follicle reserve pool and the presence of multinucleated giant cells, with lipofuscin accumulation and the emission of autofluorescence, were observed in the ovaries of the mature animals of both species. Our results support the interest in the use of the ovine and the caprine model, that share physiological and pathophysiological characteristics with humans, in future studies addressing ovarian ageing.

Mycobacteriosis, mostly resulting from Mycobacterium tuberculosis (MTb), nontuberculous mycobacteria (NTM), and Mycobacterium leprae (M. leprae), is the long-standing granulomatous disease that ravages several organs including skin, lung, and peripheral nerves, and it has a spectrum of clinical-pathologic features based on the interaction of bacilli and host immune response. Histiocytes in infectious granulomas mainly consist of infected and uninfected macrophages (Mφs), multinucleated giant cells (MGCs), epithelioid cells (ECs), and foam cells (FCs), which are commonly discovered in lesions in patients with mycobacteriosis. Granuloma Mφ polarization or reprogramming is the crucial appearance of the host immune response to pathogen aggression, which gets a command of endocellular microbe persistence. Herein, we recapitulate the current gaps and challenges during Mφ polarization and the different subpopulations of mycobacteriosis.

Background: Gingival overgrowth is a common clinical finding that most often represents reactive hyperplasia as a result of inflammatory gingival disease related to dental plaque. Irritation fibroma (IF), pyogenic granuloma (PG), peripheral ossifying fibroma (POF), and peripheral giant cell granuloma (PGCG) are non-neoplastic enlargements of the gingiva that are categorized as reactive hyperplastic lesions. Most of these lesions have a similar clinical appearance, i.e., a sessile or pedunculated nodule at the interdental papilla; the color varies from pale pink to red. All reactive gingival lesions show some variations in terms of gender, type, location, duration, and histologic features. Case Presentation: Here, we present a case of PGCG in a 10-year-old male with its clinical presentations as well as radiological and histological features along with the management procedure. Conclusion: Choice of treatment for our case was surgical excision, fluoride therapy, and oral hygiene maintenance. The patient remained tumor-free for 18 months and is still on regular follow-up.

Entamoeba histolytica is a protozoan parasite and a major cause of dysentery and diarrheal disease in developing countries. Disease transmission from one host to another occurs via cysts which can survive in environmental extremes and are transmitted through contaminated food and water. Recent studies in our lab identified a novel transcription factor, Encystation Regulatory Motif- Binding Protein (ERM-BP), which is responsive to NAD+ and has an important role in encystation. The key residues important for ERM-BP function were demonstrated in vitro using recombinant protein. In this study we demonstrate the in vivo functional consequences of mutations in key domains and their impact on Entamoeba encystation. Our results show that mutations in the DNA binding domain (ERM-BP-DBM) and in the nicotinamidase domain (ERM-BP-C198A) lead to protein mis-localization in both trophozoites and cysts and significantly reduce encystation efficiency. Additionally, we showed that silencing of ERM-BP significantly decreased the size and number of multi-nucleated giant cells (MGC) that form during encystation, indicating that ERM-BP functions upstream of the cellular aggregation that precedes stage conversion. Dissection of epistatic interactions between ERM-BP and a second encystation-related transcription factor, NF-Y revealed that ERM-BP is upstream of NF-Y in controlling the developmental cascade and appears to be one of the earliest regulators of development identified to date in Entamoeba. We also demonstrated that ERM-BP is upregulated during heat stress in Entamoeba, another condition which increases intracellular NAD+ levels and that overexpression of ERM-BP makes E. histolytica and E. invadens parasites more resistant to heat stress. Overexpression of ERM-BP in E. histolytica also induced the formation of cyst-like quadrinucleated cells and formation of MGCs. Overall, our work has identified an important role of ERM-BP in Entamoeba stress response and links an NAD+-responsive transcription factor to both development and heat shock response. Characterization of stress and developmental cascades are important avenues to investigate for Entamoeba, an important human parasitic pathogen.

The peripheral giant cell granuloma (PGCG) is a benign oral lesion occurring on the gingiva and alveolar ridge. It is the most common oral lesion and occurs at an average age of 30 years. The upsurge in the levels of estrogen and progesterone in pregnancy leads to a plethora of changes in various parts of human body, including the oral cavity. In the oral cavity, changes are commonly seen on the gingiva. These include pyogenic granuloma, PGCG and also peripheral ossifying fibroma, etc., The etiology of PGCG in our case might be related to hormonal alterations during the gestation period.

The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the (molecular) weight loss and the morphological and mechanical variations after immersion in SBF. The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods. Both scaffold parts kept their structural integrity, while changes in morphology were observed, especially for the PLA/G5 scaffold. Mechanical properties decreased with progressive degradation, while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds. The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds, while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization. Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers. Altogether, the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength. Furthermore, the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs, while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration. Thus, this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects. Additionally, the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.

More than half of tuberculosis cases in the world are due to resuscitation of dormant Mycobacterium tuberculosis (Mtb) sequestered into cell-derived structures called granulomas. It is fairly admitted that cytokines and more particularly Tumor Necrosis Factor (TNF)-α is critical in the control of Mtb infections and that anti-TNF-α drugs constitute one of the main risk factors for reactivation of latent Mtb infection. The aim of this study was to evaluate the role of etanercept, a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human p75 TNF receptor linked to the Fc portion of human IgG1, in an in vitro model of human tuberculous granuloma. We showed that etanercept slightly delayed the formation of granuloma and reduced the generation of multinuclear giant cells (MGCs). In addition, etanercept exacerbated the expression of M1 polarization genes but also induced interleukin (IL)-10 release. In addition, our results indicated that etanercept inhibited cell fusion in an IL-10-dependent manner. Moreover, adalimumab, a human monoclonal anti-TNF-α IgG1 inhibited MGC formation in granuloma, without altering IL-10 secretion and induced macrophage apoptosis. Taken together, our data provides new insights into the role of TNF-α blockers in MGCs formation and the impact of such immunomodulatory drugs on tuberculous granuloma maturation.

The present study evaluated the tissue response toward a resorbable collagen membrane derived from bovine achilles tendon (test group) in comparison to physiological wound healing (control group). After subcutaneous implantation in Wistar rats over 30 days, histochemical and immunohistochemical methods elucidated the cellular inflammatory response, vascularization pattern, membrane protein and cell absorbance capacity. After 30 days, the test-group induced two different inflammatory patterns. On the membrane surface, multinucleated giant cells (MNGCs) were formed after the accumulation of CD-68-positive cells (macrophages), whereas only mononuclear cells (MNCs) were found within the membrane central region. Peri-implant vascularization was significantly enhanced after the formation of MNGCs. No vessels were found within the central region of the membrane. Physiological wound healing revealed no MNGCs at any time point. These dynamic changes in the cellular reaction and vascularization within the test-group are related typical indications of a foreign body reaction. Due to the membrane-specific porosity, mononuclear cells migrated into the central region, and the membrane maintained its integrity over 30 days by showing no breakdown or disintegration. The ex vivo investigation analyzed the interaction between the membrane and a blood concentrate system, liquid platelet-rich fibrin (liquid PRF), derived from human peripheral blood and consisting of platelets, leukocytes and fibrin. PRF penetrated the membrane after just 15 min. The data question the role of biomaterial-induced MNGCs as a pathological reaction and whether this is acceptable to trigger vascularization or should be considered as an adverse reaction. Therefore, further pre-clinical and clinical studies are needed to identify the types of MNGCs that are induced by clinically approved biomaterials.

Central giant cell granuloma (CGCG) is a non-neoplastic lesion which exhibits a spectrum of clinical behavior ranging from non-aggressive to aggressive variants. The etiopathogenesis of CGCG is still not properly known. In the maxillofacial region, CGCG most commonly occurs in the jaw bones as an asymptomatic swelling. Radiographically, it presents as either unilocular or multilocular radiolucent lesions in the maxilla or mandible. Treatment of CGCG varies from local curettage to wide surgical excision depending upon the extent and progression of the lesion. This paper presents two cases of CGCG having different clinical presentation which resembled varied conditions leading to misdiagnosis (in one case), but was found to be CGCG on histopathologic examination.

ABSTRACT The focus of this study was to test the hypothesis that there would be no difference between the biocompatibility of resin-modified glass ionomer cements. Sixty male Wistar rats were selected and divided into four groups: Control Group; Crosslink Group; RMO Group and Transbond Group. The materials were inserted into rat subcutaneous tissue. After time intervals of 7, 15 and 30 days morphological analyses were performed. The histological parameters assessed were: inflammatory infiltrate intensity; reaction of multinucleated giant cells; edema; necrosis; granulation reaction; young fibroblasts and collagenization. The results obtained were statistically analyzed by the Kruskal-Wallis and Dunn test (P

Introduction: De Quervain’s Thyroiditis (DQT) is a self limiting inflammatory disease of the thyroid gland that presents with pain and sore throat. Although the diagnosis is usually made clinically, Fine Needle Aspiration (FNA) may provide assistance, particularly in excluding other thyroid lesions. Aim: The objective of this study was to reveal the cytological characteristics of DQT. Materials and Methods: We retrospectively reviewed the clinical and FNAC findings of 20 cases of DQT to find the most reliable features for a confident cytological diagnosis. Results: Among the cases reviewed, the common cytological features present in all 20 cases were follicular epithelial cells with degenerative changes and dirty background comprising of cellular debris and mixed inflammatory cells (lymphocytes and macrophages and occasional polymorphs). The next common finding observed was Multinucleated Giant Cells (MNGCs) seen in 19 cases followed by epithelioid cell clusters in 15 and colloid in 13 cases. Conclusion: Presence of follicular epithelial cells, large MNGCs and dirty background of cellular debris, mixed inflammatory cells with predominance of lymphocytes and macrophages were the most striking and consistent features for diagnosis of DQT in cytological smears. The above findings in consideration with the clinical history will help us to reach a definitive diagnosis. FNA also proves to be a useful tool in excluding other thyroid lesions with similar clinical presentations.

Giant cells are large mononucleated or multinucleated cells that are seen in a variety of physiological as well as pathological conditions. Multinucleated giant cells (MGCs) are important mediators of tissue remodeling and repair and also for removal of foreign materials and various pathogens. The commonly encountered giant cells arise from monocyte precursors, formed due to different mechanisms. Depending upon the mechanism of their formation these cells assume distinctly variable phenotypes. The giant cell lesions of oral cavity have been classified on the basis of etio-pathogenesis, the presence of which at times being pathognomic. We attempt to review the basic information regarding the mechanism of formation and morphology of giant cells and its significance in the associated giant cell lesions. Also we have tried to describe the clinical, histopathological and immunohistochemical aspects of various giant cell lesions of the oral cavity.

Peripheral giant cell granuloma (PGCG) is a non-neoplastic, tumor-like reactive lesion occurring exclusively on gingiva/alveolar crest. It is thought to arise from the periodontal ligament or the periosteum. Clinically, it bears resemblance to pyogenic granuloma, peripheral ossifying fibroma and many other peripheral lesions seen in the oral cavity, thereby histopathology is mandatory for the diagnosis of this lesion. The lesion although being relatively common, but still carries a lot of ambiguity. The ambiguity is in terms of its etiology, growth potential, biological behavior (recurrence), histogenesis of its cells and its treatment. The entity further holds significance because of its notorious behavior and its high tendency to recur. The present paper describes recurrent PGCG with a comprehensive insight of the literature on its etiology, clinical, radiological, histological, ultrastructural and molecular aspects. Special attention is given on the histogenesis of cells and their types as also on the differential diagnosis and treatment of this lesion.

Cherubism was first described by Jones in 1933 as "familial multilocular cystic disease of jaws." Renamed as cherubism in 1938 because of classical characteristics of full round cheeks and upward cast of the eyes to the angelic look of the cherubs immortalized by renaissance art. It is characterized by progressive painless bilateral swelling of jaws involving either maxilla or mandible producing chubby face. It is uncommon fibro-osseous disorder of bone. Mutation in the gene encoding SH3-binding protein 2 (SH3BP2) plays a role in the disease. There are indications that the gene SH3BP2 plays a role in regulating the increased osteoblast and osteoclast activities that are seen in normal tooth eruption and point mutations in the gene could cause pathologic activation of osteoclasts. The purpose of this paper is to present the uncommon form of cherubism and to review the clinicoradiographic, histopathologic features and treatment so as to facilitate diagnosis of disease.

Multinucleated giant cells (MGC) are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF) in association with other cytokines such as interferon-gamma (IFN-γ), tumour necrosis factor-alpha, interleukin (IL)-10 or transforming growth factor beta (TGF-β1) on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg). The generation of MGC was determined by fusion index (FI) and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18). The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18.

Introduction: Macrophages undergo fusion to form multinucleated giant cells (MGC) in several pathologic conditions. The exact mechanism of their generation is still unclear. MGC are a common feature of granulomas that develop during various inflammatory reactions. Aim: To study the histopathological features of giant cell lesions in lungs and correlate the characteristics of giant cells with other histopathological findings. Also, to determine the utility of morphometry to differentiate foreign body and Langhans MGC. Materials and Methods: Seven cases were analysed. Specimen of lungs was grossed, sectioned and processed. Routinely, tissue sections were stained by Haematoxylin and Eosin (H&E) stain. Polarizing microscopy and special stains were employed in selected cases. Granulomas and MGC were counted and measured. Several other parameters like location, distribution, type and number of MGC, associated predominant inflammatory component and nature of granulomas were analysed. Results: Five patterns of lesions were observed in seven cases. Aspiration pneumonia was seen in three cases (42.85%) and constituted the most common pattern. However, aspiration pneumonia as the only cause of MGC was seen in only one case (14.28%). Pulmonary tuberculosis and asteroid bodies constituted two cases (28.57%) each. Cryptococcal pneumonia and cholesterol clefts constituted one case (14.28%) each. Crypococci were demonstrated to be positively birefringent by polarized microscopy on Ziehl-Neelsen stained sections. Based on statistical analysis of morphometric data, a new index (NP index) was proposed to statistically categorize MGC into foreign body type and Langhans type. NP index value of ≤0.016 was found to be statistically significant (p