Blockade of the kallikrein-kinin system reduces endothelial complement activation in vascular inflammation
| Autor: | Davalieva, Katarina, Makridakis, Manousos, Vlahou, Antonia, Frantzi, Maria, Boizard, Franck, Moussaoui, Nabila, Lescat, Ophélie, Fedou, Camille, Feuillet, Guylène, Casemayou, Audrey, Neau, Eric, Decatte, Luc, Raaijmakers, Anke, Vayssière, Christophe, Goua, Valérie, Lucas, Charlotte, Benachi, Alexandra, Delmas, Hélène Laurichesse, Allain-Launay, Emma, Boudailliez, Bernard, Simon, Elisabeth, Noel, Catherine, Floch, Corinne, Bourdat-Michel, Guylène, Weingertner, Anne-Sophie, Oury, Jean-François, Baudouin, Véronique, Bory, Jean-Paul, Pietrement, Christine, Fiorenza, Maryse, Kessler, Sylvie, Auriol, Françoise Conte, Marcorelles, Pascale, Collardeau-Frachon, Sophie, Magalhães, Pedro, Batut, Julie, Blader, Patrick, Saulnier Blache, Jean-Sebastien, Allegaert, Karel, Aubard, Yves, Basmaison, Odile, Benevent, Jean-Baptiste, Biquard, Florence, Champion, Gérard, Delbosc, Jean-Marie, Eckart, Philippe, Gaucherand, Pascal, Guigonis, Vincent, Hougas, Blandine, Martin, Alain, Martin, Sophie, Maupin-Hyvonnet, Mariannick, Merveille, Marina, Mousty, Eve, Nobili, François, Taque, Sophie, Latosinska, Agnieszka, Faguer, Stanislas, Beige, Joachim, van der Zanden, Loes, Levtchenko, Elena, Moulos, Panogiotis, Lounis, Nadia, Conte-Auriol, Françoise, Olsen, Henning, Hindryckx, An, De Catte, Luc, Vayssieres, Christophe, Sartor, Agnes, Groussolles, Marion, Plard, Christelle, Guerby, Paul, Connan, Laure, Morin, Mathieu, Simon, Elizabeth, Breaud, Jean, Saliou, Anne-Hélène, De Parscau, Loic, Jay, Nadine, Germouty, Isabelle, Le Bouar, Gwenaelle, Ryckewaert, Amelie, Manca-Pellissier, Marie-Christine, Merrot, Thierry, Laurichesse, Helene, Gallot, Denis, Bessenay, Lucie, Bidat, Laurent, Boize, Philippe, Winer, Norbert, Allain-Launey, Emma, Le Vaillant, Claudine, Prieur, Fabienne, Lavocat, Marie-Pierre, Coatleven, Frederic, Debromez, Eric, Harembat, Jérôme, Llanas, Brigitte, Favre, Romain, Moog, Raphael, Zaloszyc, Ariane, Massardier, Jérôme, DEMEDE, Delphine, Perrotin, Franck, Cloarec, Sylvie, Vequeau-Goua, Valérie, Descombes, Emmanuelle, Boulot, Pierre, Morin, Denis, Fuchs, Florent, Tenenbaum, Julie, Ville, Yves, Blanc, Thomas, Heidet, Laurence, Paris, Anne, Dobremez, Eric, Froute, Marie-Françoise, Gondry, Jean, Muszynski, Charles, Haraux, Elodie, Lobelle, Fabienne, Chevreau, Julien, Rosenblatt, Jonathan, Baudoin, Véronique, Deschenes, Georges, Guigue, Virginie, Amblard, Florence, Bourdat-Michel, Guylhène, Wühl, Elke, Schaefer, Franz, Elsässer, Michael, Persico, Nicola, Rossi, Federica, Manzoni, Gianantonio, De Marco, Erika, Montini, Giovanni, Capone, Valentina, Caforio, Leonardo, Zaccara, Antonio, Innocenzi, Michele, Bagolan, Pietro, Capozza, Nicola, Castagnetti, Marco, Mancini, Mariangela, Oepkes, Dick, van Scheltema, Phebe Adama, Feitz, Wout, Kortmann, Barbara, Schreuder, Michiel, Pawłowska, Barbara, Fortecka-Piestrzeniewicz, Katarzyna, Olejniczak, Dariusz, Ariceta, Gema, Arevalo, Silvia, RODO, Carlota, Fossum, Magdalena, Lindgren, Peter, Parvex, Paloma, Chehade, Hassib, He, Tianlin, Metzger, Jochen, Mullen, William, Mischak, Harald, Zürbig, Petra, Jankowski, Vera, Buffin-Meyer, Bénédicte, Tkaczyk, Marcin, Stańczyk, Małgorzata, Breuil, Benjamin, Siwy, Justyna, Szaflik, Krzysztof, Talar, Tomasz, Wojtera, Justyna, Krzeszowski, Waldemar, Decramer, Stéphane, Lopatko Fagerström, Ingrid, Ståhl, Anne-lie, Mossberg, Maria, Tati, Ramesh, Kristoffersson, Ann-Charlotte, Kahn, Robin, Bascands, Jean-Loup, Klein, Julie, Schanstra, Joost, Segelmark, Mårten, Karpman, Diana |
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| Přispěvatelé: | Department of Pediatrics [Lund, Sweden] (Clinical Sciences), Lund University [Lund], Wallenberg Center for Molecular Medicine [Lund, Sweden], Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Nephrology [Lund, Sweden] (Clinical Sciences Lund), Department of Medical and Health Sciences [Lund, Sweden], Linköping University (LIU), The study was supported by The Swedish Research Council (K2015-99X-22877-01-6 and 2017-01920), The Knut and Alice Wallenberg Foundation (Wallenberg Clinical Scholar 2015.0320), The Torsten Söderberg Foundation, Skåne Centre of Excellence in Health, IngaBritt och Arne Lundberg's Research Foundation, Crown Princess Lovisa's Society for Child Care, Region Skåne and The Konung Gustaf V:s 80-årsfond (all to DK). Alfred Österlund Foundation (to LMFLL and RK). TheWallenberg Center forMolecular Medicine, The Swedish RheumatismAssociation, The Anna-Greta Crafoord Foundation, Greta and Johan Kock's Foundation, the Samariten Foundation, Fanny Ekdahl foundation, the Jerring foundation and the Thelma Zoegas Foundation (to RK). JPS and JK were partially funded by a grant from the 'Fondation pour la Recherche Médicale' (grant number DEQ20170336759). MS was funded by The Swedish Rheumatism Association and the Ingrid Asp Foundation., Schanstra, Joost, Macedonian Academy of Sciences and Arts [Skopje, North Macedonia] (MASA), Biomedical Research Foundation of the Academy of Athens (BRFAA), Mosaiques Diagnostics & Therapeutics (MOSAIQUES DIAGNOSTICS & THERAPEUTICS), Mosaiques Diagnostics & Therapeutics AG, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], KfH-Nierenzentrum und Klinikum St. Georg, Nephrologie, Leipzig, Radboud University Medical Center [Nijmegen], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), HybridStat Predictive Analytics [Athens, Greece], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Leuven [Leuven], Heidelberg University Hospital [Heidelberg], University of Milan, Mosaiques Diagnostics GmbH [Hanovre, Allemagne], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), RWTH Aachen University, Polish Mother’s Memorial Hospital Research Institute [Lodz] (ICZMP), Mosaiques Diagnostics GmbH [Hannover, Germany], Mosaiques Diagnostics and Therapeutics AG [Hannover, Germany], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Université Fédérale Toulouse Midi-Pyrénées |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Research paper Mouse Kallikrein-Kinin System [SDV]Life Sciences [q-bio] Pharmacology Kidney Mice 0302 clinical medicine Glomerular C3 deposition Cell-Derived Microparticles Complement Activation Cells Cultured Chemistry General Medicine Kinin Middle Aged Receptor antagonist 3. Good health [SDV] Life Sciences [q-bio] medicine.anatomical_structure 030220 oncology & carcinogenesis Female medicine.symptom Endothelial microvesicles Complement C1 Inhibitor Protein Protein Binding Vasculitis Complement Radiology Nuclear Medicine and Medical Imaging Adult Endothelium medicine.drug_class Inflammation Bradykinin General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Classical complement pathway medicine Animals Humans Aged Endothelial Cells Biological Transport Complement System Proteins Microvesicles Complement system Disease Models Animal 030104 developmental biology Immunoglobulin G Endothelium Vascular Radiologi och bildbehandling |
| Zdroj: | EBioMedicine EBioMedicine, 2019, 47, pp.319-328. ⟨10.1016/j.ebiom.2019.08.020⟩ EBioMedicine, Elsevier, 2019, 47 (3), pp.319-328. ⟨10.1016/j.ebiom.2019.08.020⟩ EBioMedicine, Elsevier, 2019, 47, pp.319-328. ⟨10.1016/j.ebiom.2019.08.020⟩ |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2019.08.020⟩ |
| Popis: | Background: The complement and kallikrein-kinin systems (KKS) are activated during vascular inflammation. The aim of this study was to investigate if blockade of the KKS can affect complement activation on the endothelium during inflammation. Methods: Complement deposition on endothelial microvesicles was assayed in vasculitis patient plasma samples and controls. Plasma was perfused over glomerular endothelial cells and complement deposition assayed by flow cytometry. The effect of the kinin system was assessed using kinin receptor antagonists and C1-inhibitor. The in vivo effect was assessed in kidney sections from mice with nephrotoxic serum-induced glomerulonephritis treated with a kinin receptor antagonist. Findings: Vasculitis patient plasma had significantly more C3- and C9-positive endothelial microvesicles than controls. Perfusion of patient acute-phase plasma samples over glomerular endothelial cells induced the release of significantly more complement-positive microvesicles, in comparison to remission or control plasma. Complement activation on endothelial microvesicles was reduced by kinin B1- and B2-receptor antagonists or by C1-inhibitor (the main inhibitor of the classical pathway and the KKS). Likewise, perfusion of glomerular endothelial cells with C1-inhibitor-depleted plasma induced the release of complement-positive microvesicles, which was significantly reduced by kinin-receptor antagonists or C1-inhibitor. Mice with nephrotoxic serum-induced glomerulonephritis exhibited significantly reduced glomerular C3 deposition when treated with a B1-receptor antagonist. Interpretation: Excessive complement deposition on the endothelium will promote endothelial injury and the release of endothelial microvesicles. This study demonstrates that blockade of the KKS can reduce complement activation and thereby the inflammatory response on the endothelium. (C) 2019 The Authors. Published by Elsevier B.V. Funding Agencies|Swedish Research CouncilSwedish Research Council [K2015-99X-22877-01-6, 2017-01920]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [2015.0320]; Torsten Soderberg Foundation; Skane Centre of Excellence in Health; Crown Princess Lovisas Society for Child Care; Konung Gustaf V:s 80-arsfond; Alfred Osterlund Foundation; Wallenberg Center for Molecular Medicine; Swedish Rheumatism Association; Anna-Greta Crafoord Foundation; Greta and Johan Kocks Foundation; Samariten Foundation; Fanny Ekdahl foundation; Jerring foundation; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale [DEQ20170336759]; Ingrid Asp Foundation; IngaBritt och Arne Lundbergs Research Foundation; Region Skane; Thelma Zoegas Foundation |
| Databáze: | OpenAIRE |
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