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1. Déterminants de l’inquiétude des patients avant la réalisation des explorations fonctionnelles respiratoires

Author

Ben Ali, Y., primary, Verrier, M., additional, Moreno, A., additional, Groutteau, S., additional, Bikoko, E., additional, Lambeau, G., additional, Kherbouche, A., additional, Sueur, H., additional, Lautredou, C., additional, Letournel, M., additional, Planès, C., additional, Chauveau, S., additional, Sesé, L., additional, and Gille, T., additional

Published
2024
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2. Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Author

Sethi, S., Beck LH, J.r., Glassock, R.J., Haas, Mark, Vriese, A.S. de, Caza, T.N., Hoxha, E., Lambeau, G., Tomas, N.M., Madden, B., Debiec, H., D'Agati, V.D., Alexander, M.P., Amer, H., Appel, G.B., Barbour, S.J., Caravaca-Fontan, F., Cattran, D.C., Casal Moura, M., D'Avila, D.O., Eick, R.G., Garovic, V.D., Greene, E.L., Herrera Hernandez, L.P., Jennette, J.C., Lieske, J.C., Markowitz, G.S., Nath, K.A., Nasr, S.H., Nast, C.C., Pani, A., Praga, M., Remuzzi, G., Rennke, H.G., Ruggenenti, P., Roccatello, D., Soler, M.J., Specks, U., Stahl, R.A.K., Singh, R.D., Theis, J.D., Velosa, J.A., Wetzels, J.F.M., Winearls, C.G., Yandian, F., Zand, L., Ronco, P., Fervenza, F.C., Sethi, S., Beck LH, J.r., Glassock, R.J., Haas, Mark, Vriese, A.S. de, Caza, T.N., Hoxha, E., Lambeau, G., Tomas, N.M., Madden, B., Debiec, H., D'Agati, V.D., Alexander, M.P., Amer, H., Appel, G.B., Barbour, S.J., Caravaca-Fontan, F., Cattran, D.C., Casal Moura, M., D'Avila, D.O., Eick, R.G., Garovic, V.D., Greene, E.L., Herrera Hernandez, L.P., Jennette, J.C., Lieske, J.C., Markowitz, G.S., Nath, K.A., Nasr, S.H., Nast, C.C., Pani, A., Praga, M., Remuzzi, G., Rennke, H.G., Ruggenenti, P., Roccatello, D., Soler, M.J., Specks, U., Stahl, R.A.K., Singh, R.D., Theis, J.D., Velosa, J.A., Wetzels, J.F.M., Winearls, C.G., Yandian, F., Zand, L., Ronco, P., and Fervenza, F.C.

Abstract

Contains fulltext : 300117.pdf (Publisher’s version ) (Open Access), Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment., 01 december 2023

Published
2023

4. What are the mechanisms of gastrointestinal lipases adsorption onto heterogenous biomimetic vegetal membranes?

Author

Kergomard, Jeanne, Carrière, F, Lambeau, G, Paboeuf, Gilles, Barouh, Nathalie, Villeneuve, Pierre, Bourlieu-Lacanal, Claire, Vié, V., Kergomard, Jeanne, Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Démarche intégrée pour l'obtention d'aliments de qualité (UMR QualiSud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier

Subjects
[PHYS]Physics [physics], [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [PHYS.COND] Physics [physics]/Condensed Matter [cond-mat], [PHYS] Physics [physics]
Abstract

International audience; Gastrointestinal lipases are crucial for lipid hydrolysis and must get adsorbed onto the substrate interface prior lipolysis. Such adsorption had not been deeply investigated on biomimetic vegetal membranes. Our objective was thus to characterize such adsorption and lipolysis using complementary biophysical tools (tensiometry, ellipsometry, atomic force microscopy) and in vitro digestion.Heterogenous monolayers based on galactolipids, phospholipids, and phytosterols were used. Four lipases were studied: i) gastric lipase (GL), ii) pancreatic lipase 2 (PLRP2), (iii) pancreatic triacylglycerol lipase and its cofactor, colipase (PTL/coPTL), and (iv) pancreatic secreted phospholipase A2 (sPLA2-IB).A strong surfactant property of GL and its preferential adsorption onto expanded lipid phase and at the phase boundary were observed, in line with previous results on milk fat globule membrane. With PLRP2, changes in surface pressure indicated a lipolytic activity. Such variation was not observed upon PTL/coPTL adsorption, and may be related to the absence of activity of PTL on polar lipids. The injection of sPLA2-IB did not indicate a clear trend of lipolysis on the lipid film but changed the morphology of condensed domains.This study is a step forward to understand the interactions of gastrointestinal lipases with plant lipid membranes, an overlooked aspect of lipid digestion

Published
2022

6. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy

Author

Fernández-Juárez, G., Rojas-Rivera, J., Logt, A. van de, Justino, J., Sevillano, A., Caravaca-Fontán, F., Ávila, A., Rabasco, C., Cabello, V., Varela, A., Díez, M., Martín-Reyes, G., Diezhandino, M.G., Quintana, L.F., Agraz, I., Gómez-Martino, J.R., Cao, M., Rodríguez-Moreno, A., Rivas, B., Galeano, C., Bonet, J., Romera, A., Shabaka, A., Plaisier, E., Espinosa, M., Egido, J., Segarra, A., Lambeau, G., Ronco, P., Wetzels, J., Praga, M., Fernández-Juárez, G., Rojas-Rivera, J., Logt, A. van de, Justino, J., Sevillano, A., Caravaca-Fontán, F., Ávila, A., Rabasco, C., Cabello, V., Varela, A., Díez, M., Martín-Reyes, G., Diezhandino, M.G., Quintana, L.F., Agraz, I., Gómez-Martino, J.R., Cao, M., Rodríguez-Moreno, A., Rivas, B., Galeano, C., Bonet, J., Romera, A., Shabaka, A., Plaisier, E., Espinosa, M., Egido, J., Segarra, A., Lambeau, G., Ronco, P., Wetzels, J., and Praga, M.

Abstract

Item does not contain fulltext, A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy tha

Published
2021

16. Progesterone-induced acrosome exocytosis requires sequential involvement of calcium-independent phospholipase A2β (iPLA2β) and group X secreted phospholipase A2 (sPLA2)

Author

Nahed, R.A. Martinez, G. Escoffier, J. Yassine, S. Karaouzène, T. Hograindleur, J.-P. Turk, J. Kokotos, G. Ray, P.F. Bottari, S. Lambeau, G. Hennebicq, S. Arnoult, C.

Abstract

Phospholipase A2 (PLA2) activity has been shown to be involved in the sperm acrosome reaction (AR), but the molecular identity of PL A2 isoforms has remained elusive. Here, we have tested the role of two intracellular (iPL A2 β and cytosolic PL A2 α) and one secreted (group X) PLA2s in spontaneous and progesterone (P4)-induced AR by using a set of specific inhibitors and knock-out mice. iPL A2β is critical for spontaneous AR, whereas both iPL A2 β and groupXsecreted PL A2 are involved in P4-induced AR. Cytosolic PL A2 α is dispensable in both types of AR. P4-induced AR spreads over 30 min in the mouse, and kinetic analyses suggest the presence of different sperm subpopulations, using distinctPL A2 pathways to achieve AR. At low P4 concentration (2M), sperm undergoing early AR (0-5 min post-P4) rely on iPL A2 β , whereas sperm undergoing late AR (20-30 min post-P4) rely on group X secreted PL A2. Moreover, the role of PL A2 s in AR depends on P4 concentration, with the PLA2s being key actors at low physiological P4 concentrations (

Published
2016

17. Production of vascular endothelial growth factors from human lung macrophages induced by group IIA and group X secreted phospholipases A2

Author

GRANATA, FRANCESCOPAOLO, MARONE, GIANNI, TRIGGIANI, MASSIMO, Frattini A, Loffredo S, Staiano RI, Petraroli A, Ribatti D, Oslund R, Gelb MH, Lambeau G, LOFFREDO, STEFANIA, Division of Clinical Immunology and Allergy, Università degli studi di Napoli Federico II, Department of Human Anatomy and Histology, Università degli studi di Bari Aldo Moro (UNIBA), Department of Chemistry, University of Washington [Seattle], Department of Biochemistry [Washington ], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Granata, Francescopaolo, Frattini, A, Loffredo, S, Staiano, Ri, Petraroli, A, Ribatti, D, Oslund, R, Gelb, Mh, Lambeau, G, Marone, Gianni, Triggiani, Massimo, and Loffredo, Stefania

Subjects
Vascular Endothelial Growth Factor A, MESH: Macrophages, Alveolar, MESH: Group X Phospholipases A2, Angiogenesis, Vascular Endothelial Growth Factor C, Chick Embryo, MESH: Protein Isoforms, MESH: Vascular Endothelial Growth Factors, Chorioallantoic Membrane, MESH: Lymphangiogenesis, 0302 clinical medicine, Protein Isoforms, Immunology and Allergy, MESH: Animals, Lymphangiogenesis, Receptor, Lung, 0303 health sciences, Neovascularization, Pathologic, Vascular Endothelial Growth Factors, MESH: Chick Embryo, MESH: Group II Phospholipases A2, Vascular endothelial growth factor A, Chorioallantoic membrane, Vascular endothelial growth factor C, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Inflammation Mediators, medicine.symptom, MESH: Neovascularization, Physiologic, Immunology, MESH: Inflammation Mediators, Neovascularization, Physiologic, Inflammation, MESH: Receptor, Adenosine A3, Biology, Group II Phospholipases A2, Article, Catalysis, 03 medical and health sciences, Macrophages, Alveolar, medicine, Animals, Group X Phospholipases A2, Humans, MESH: Lung, 030304 developmental biology, MESH: Chorioallantoic Membrane, MESH: Humans, MESH: Vascular Endothelial Growth Factor A, Receptor, Adenosine A3, MESH: Vascular Endothelial Growth Factor C, MESH: Catalysis, Cancer research, MESH: Neovascularization, Pathologic
Abstract

Angiogenesis and lymphangiogenesis mediated by vascular endothelial growth factors (VEGFs) are main features of chronic inflammation and tumors. Secreted phospholipases A2 (sPLA2s) are overexpressed in inflammatory lung diseases and cancer and they activate inflammatory cells by enzymatic and receptor-mediated mechanisms. We investigated the effect of sPLA2s on the production of VEGFs from human macrophages purified from the lung tissue of patients undergoing thoracic surgery. Primary macrophages express VEGF-A, VEGF-B, VEGF-C, and VEGF-D at both mRNA and protein level. Two human sPLA2s (group IIA and group X) induced the expression and release of VEGF-A and VEGF-C from macrophages. Enzymatically-inactive sPLA2s were as effective as the active enzymes in inducing VEGF production. Me-Indoxam and RO092906A, two compounds that block receptor-mediated effects of sPLA2s, inhibited group X-induced release of VEGF-A. Inhibition of the MAPK p38 by SB203580 also reduced sPLA2-induced release of VEGF-A. Supernatants of group X-activated macrophages induced an angiogenic response in chorioallantoic membranes that was inhibited by Me-Indoxam. Stimulation of macrophages with group X sPLA2 in the presence of adenosine analogs induced a synergistic increase of VEGF-A release and inhibited TNF-α production through a cooperation between A2A and A3 receptors. These results demonstrate that sPLA2s induce production of VEGF-A and VEGF-C in human macrophages by a receptor-mediated mechanism independent from sPLA2 catalytic activity. Thus, sPLA2s may play an important role in inflammatory and/or neoplastic angiogenesis and lymphangiogenesis.

Published
2010
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19. Identification of Epithelial Phospholipase A2 Receptor 1 as a Potential Target in Asthma

Author

Nolin, J., Ogden, H., Lai, Y., Altemeier, W., Frevert, C., Bollinger, J., Naika, G., Kicic, Anthony, Stick, S., Lambeau, G., Henderson, W., Gelb, M., Hallstrand, T., Nolin, J., Ogden, H., Lai, Y., Altemeier, W., Frevert, C., Bollinger, J., Naika, G., Kicic, Anthony, Stick, S., Lambeau, G., Henderson, W., Gelb, M., and Hallstrand, T.

Abstract

Secreted phospholipase A 2 s (sPLA 2 s) regulate eicosanoid formation and have been implicated in asthma. Although sPLA 2 s function as enzymes, some of the sPLA 2 s bind with high affinity to a C-type lectin receptor, called PLA 2 R1, which has functions in both cellular signaling and clearance of sPLA 2 s. We sought to examine the expression of PLA 2 R1 in the airway epithelium of human subjects with asthma and the function of the murine Pla2r1 gene in a model of asthma. Expression of PLA 2 R1 in epithelial brushings was assessed in two distinct cohorts of children with asthma by microarray and quantitative PCR, and immunostain ing for PLA 2 R1 was conducted on endobronchial tissue and epithelial brushings from adults with asthma. C57BL/129 mice deficient in Pla2r1 (Pla2r1 -/- ) were characterized in an ovalbumin (OVA) model of allergic asthma. PLA 2 R1 was differentially overexpressed in epithelial brushings of children with atopic asthma in both cohorts. Immunostaining for PLA 2 R1 in endobronchial tissue localized to submucosal glandular epithelium and columnar epithelial cells. After OVA sensitization and challenge, Pla2r1 -/- mice had increased airway hyperresponsiveness, as well as an increase in cellular trafficking of eosinophils to the peribronchial space and bronchoalveolar lavage fluid, and an increase in airway permeability. In addition, Pla2r1 -/- mice had more dendritic cells in the lung, higher levels of OVAspecific IgG, and increased production of both type-1 and type-2 cytokines by lung leukocytes. PLA 2 R1 is increased in the airway epithelium in asthma, and serves as a regulator of airway hyperresponsiveness, airway permeability, antigen sensitization, and airway inflammation.

Published
2016

23. 1,3,5-Triazepan-2,6-diones as conformationally constrained dipeptide mimetics. In silico guided identification of sPLA2 inhibitors

Author

Gilles Guichard, Lena, G., Boeglin, J., Muller, P., Boilard, E., Lambeau, G., Rognan, D., Didierjean, C., Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Bioinformatique du médicament (CNRS UMR 7081), Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Structures Formelles du Langage (SFL), and Université Paris Lumières (UPL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 8 Vincennes-Saint-Denis (UP8)

Subjects
[CHIM.THER]Chemical Sciences/Medicinal Chemistry, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2009

24. Structure and function comparison of Micropechis ikaheka snake venom phospholipase A isoenzymes

Author

Lok, S.M., Gao, R., Rouault, M., Lambeau, G., Gopalakrishnakone, P., Swaminathan, K., Institute of Molecular and Cell Biology, Singapour, Department of Anatomy, National University of Singapore (NUS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), and Department of Biological Sciences [Singapore]

Published
2005

25. Characterization and differentiation-dependent regulation of secreted phospholipases A2 in human primary keratinocytes and in healthy and psoriatic human skin

Author

Haas, U., Podda, M., Gurrieri, S., Alonso, A., Furstenberger, S., Pfeilschifter, J., Lambeau, G., H. Gelb, M., Kaszkin, M., Pharmazentrum Frankfurt, University Hospital, Center of Dermatology and Venerology, Applied Tumor Virology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Tumor Cell Regulation, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Departements of Chemistry and Biochemistry, and Seattle University [Seattle]

Published
2005

29. Novel mammalian group XII secreted phospholipase A2 lacking enzymatic activity

Author

Rouault, M., Bollinger, J., Lazdunski, M., H. Gelb, M., Lambeau, G., Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Departements of Chemistry and Biochemistry, and Seattle University [Seattle]

Published
2003

30. Cellular arachidonate-releasing function of novel classes of secretory phospholipase A2s (group III and XII)

Author

Murakami, M., Masuda, S., Shimbara, S., Bezzine, S., Lazdunski, M., Lambeau, G., H. Gelb, M., Matsukura, S., Kokubu, F., Adachi, M., Kudo, I., Department of Health Chemistry School of Pharmaceutical Sciences, Showa University, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Departements of Chemistry and Biochemistry, Seattle University [Seattle], and First Department of Internal Medicine, School of Medicine

Published
2003

31. Potentiation of TNFalpha -induced sPLA2-IIA expression in mesangial cells by an autocrine loop involving secreted phospholipase A2 and PPARalpha activation

Author

Beck, S., Lambeau, G., Scholz-Pedretti, K., H. Gelb, M., Janssen, M.J., Edwards, S.H., Wilton, D.C., Pfeilschifter, J., Kaszkin, M., Pharmazentrum Frankfurt, University Hospital, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Departements of Chemistry and Biochemistry, Seattle University [Seattle], Department of Clinical Chemistry, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Division of Biochemistry and Molecular Biology School of Biological Sciences, and University of Southampton

Published
2003

32. Groups IV, V and X phospholipases A2 in human neutrophils. Role in eicosanoid production and gram negative bacterial phospholipid hydrolysis

Author

Degousee, N., Ghomashchi, F., Stefanski, E., Singer, A., P. Smart, B., Borregaard, N., Reithmeier, R., F. Lindsay, T., Lichtenberger, C., Reinisch, W., Lambeau, G., Arm, J., Tischfield, J., H. Gelb, M., B. Rubin, B., Division of Vascular Surgery, Max Bell Research Center-Toronto General Hospital-University Health Network, Departements of Chemistry and Biochemistry, Seattle University [Seattle], Granulocyte Research Laboratory Department of Hematology, Copenhagen University Hospital, Medical Research Council Group in Membrane Biology Departments of Medicine and Biochemistry Medical Science Building, University of Toronto, Clinic of Internal Medicine IV, Department of Gastroenterology and Hepathology, Universität Wien, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, Rutgers, Rutgers, The State University of New Jersey [New Brunswick] (RU), and Rutgers University System (Rutgers)-Rutgers University System (Rutgers)

Published
2002

33. Secreted phospholipase A2 potentiates glutamate-induced calcium increase and cell death in primary neuronal cultures

Author

Decoster, M.A., Lambeau, G., Lazdunski, M., Bazan, N.G., Neuroscience Center of Excellence, LSU Health Sciences Center, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Published
2002

34. Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy

Author

Dahnrich, C., Komorowski, L., Probst, C., Seitz-Polski, B., Esnault, V., Wetzels, J.F.M., Hofstra, J.M., Hoxha, E., Stahl, R.A.K., Lambeau, G., Stocker, W., Schlumberger, W., Dahnrich, C., Komorowski, L., Probst, C., Seitz-Polski, B., Esnault, V., Wetzels, J.F.M., Hofstra, J.M., Hoxha, E., Stahl, R.A.K., Lambeau, G., Stocker, W., and Schlumberger, W.

Abstract

Item does not contain fulltext, BACKGROUND: Autoantibodies against the M-type phospholipase A2 receptor (PLA2R1) are specific markers for primary membranous nephropathy (pMN) and anti-PLA2R1 serum levels may be useful to monitor disease activity. So far, a recombinant cell-based indirect immunofluorescence assay (RC-IFA) using recombinant PLA2R1 as a substrate has been widely available but lacks a finely graduated assessment of antibody concentrations. METHODS: In order to setup a standardized ELISA, the extracellular domain of human PLA2R1 was expressed in HEK293. The purified protein was used to form the solid-phase in an ELISA which was then employed to analyze sera from 200 patients with primary MN, 27 patients with secondary MN, 230 patients with other glomerular diseases, 316 patients with systemic autoimmune diseases, and from 291 healthy blood donors. RESULTS: At a set specificity of 99.9% the sensitivity of the anti-PLA2R1 IgG ELISA was found to be 96.5%. A similar sensitivity (98.5%) was obtained when binding of only subclass IgG4 was analyzed. The calibrated assay showed a good class correlation with the results of the RC-IFA, was robust and could be stored for several months without any loss of quality. CONCLUSION: The results demonstrate that the new test system is qualified for routine use and that it has an almost perfect agreement with both, the clinical characterization of the patients and the results generated with RC-IFA.

Published
2013

42. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

Author

Kolko, M, Bruhn, T, Christensen, Thomas, Lazdunski, M, Lambeau, G, Bazan, N G, Diemer, Nils Henrik, Kolko, M, Bruhn, T, Christensen, Thomas, Lazdunski, M, Lambeau, G, Bazan, N G, and Diemer, Nils Henrik

Abstract

The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10 and 20 pmol OS2 caused no neurological abnormalities or tissue damage. OS2 (50 pmol) caused apathy and circling towards the injection side. Histology revealed an infarct at the injection site. Injection of 50 pmol OS1 showed very little or no signs of neurotoxicity. Injection of 2.5 micromol Glu caused no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards the side of injection in the following days. Thus, OS2 greatly potentiates glutamate excitoxicity in vivo.

Published
1999

49. T-cell and antibody responses to phospholipase A2 from different species show distinct cross-reactivity patterns.

Author

Sin, B. A., Akdis, M., Zumkehr, J., Bezzine, S., Bekpen, C., Lambeau, G., and Akdis, C. A.

Subjects
MEDICAL research, IMMUNOGLOBULIN G, IMMUNE response, ENZYME-linked immunosorbent assay, EPITOPES, T cells, LYMPHOCYTES
Abstract

To cite this article: Sin BA, Akdis M, Zumkehr J, Bezzine S, Bekpen C, Lambeau G, Akdis CA. T-cell and antibody responses to phospholipase A2 from different species show distinct cross-reactivity patterns. Allergy 2011; 66: 1513-1521. Abstract Background: Secreted phospholipases A2 (sPLA2) represent antigens to which humans may be rarely or frequently exposed. Thus, the investigation of humoral and cellular immune responses to sPLA2s from different species can provide a suitable model in the study of antibody and T-cell cross-reactivity. Methods: Specific IgE, IgG1, IgG4, and IgA antibodies were analyzed by ELISA against sPLA2s from pancreas of Bos taurus (BT), Apis mellifera (AM) bee venom, Daboia russellii (DR) and Naja mossambica (NM) snake venoms, and human group III (hGIII) sPLA2 using sera of nonallergic beekeepers, AM-allergic patients, and healthy controls. T-cell cross-reactivity was investigated in PBMC, and T-cell clones (TCC) are generated against AM sPLA2. Results: Hyperimmune and allergic individuals showed high levels of sPLA2-specific IgG4 and significant IgG4 cross-reactivity between BT, DR, and NM sPLA2s. Furthermore, IgE, IgA, and IgG1 cross-reactivities against BT, DR, and NM sPLA2s were also detectable in the range of 22.2-44.8%. Allergic patients showed significant T-cell proliferative response to NM sPLA2 together with increased IFN-γ and IL-13 production even though they had never been exposed to cobra venom. Although nonallergic healthy controls show no cross-reactivity at T-cell level, they did have low levels of IgG4 and IgA against BT, DR, and NM sPLA2s. Human TCC spanning three major T-cell epitopes of AM sPLA2 showed minor proliferative response to NM and hGIII sPLA2s. Conclusions: This study shows that T cells and antibodies may show cross-reactivity between different species without being naturally exposed to sPLA2s. [ABSTRACT FROM AUTHOR]

Published
2011
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