%0 Journal Article %T CD32A-expressing platelets determine the severity of experimental anaphylaxis. %+ Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology %+ Sorbonne Université - Faculté de Médecine (SU FM) %+ Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP) %+ Université Paris Diderot - Paris 7 (UPD7) %+ Laboratoire d'Immunologie "Autoimmunité et Hypersensibilités" [AP-HP Hôpital Bichat, Paris] %+ Cytokines, chimiokines et immunopathologie %+ Département d'Anesthésie Réanimation [CHU Bichat-Claude-Bernard] %+ Regeneron Pharmaceuticals [Tarrytown] %+ Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)) %A Beutier, Héloïse %A Hechler, Béatrice %A Godon, Ophélie %A Wang, Yu %A Gillis, Caitlin M. %A de Chaisemartin, Luc %A Gouel-Chéron, Aurélie %A Magnenat, Stéphanie %A Macdonald, Lynn, E %A Murphy, Andrew, J %A Chollet-Martin, Sylvie %A Longrois, Dan %A Gachet, Christian %A Bruhns, Pierre %A Jönsson, Friederike %Z We are thankful to our colleagues F. Abdallah, B. Iannascoli, and O. Richard-Le Goff at Institut Pasteur (Paris) for technical help. We are thankful to our colleagues for their gifts: M. P. Reilly and S. McKenzie (Jefferson Medical College, Philadelphia, PA) for FCGR2A transgenic mice and LFB Biomédicaments (Les Ulis, France) for human albumin and fibrinogen. Funding: This work was supported by the European Research Council (ERC)–Seventh Framework Program (ERC-2013-CoG 616050), by a Jeunes Chercheuses/Jeunes Chercheurs grant from the Agence National de la Recherche (ANR-16-CE15-0012-01), the Institut Pasteur, INSERM, the Société Française d’Allergologie (Soutien de la Recherche en Allergologie), and the Etablissement Français du Sang. H.B. was supported by a fellowship from the Université Pierre et Marie Curie. C.M.G. was supported partly by a stipend from the Pasteur-Paris University (PPU) International PhD program, by the Institut Carnot Pasteur Maladies Infectieuses, and partly by the Balsan company. Y.W. is part of the PPU International PhD Program that received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement no. 665807 and from the Labex Milieu Intérieur, Institut Pasteur. A.G.-C. benefited from a stipend provided by Assistance Publique–Hôpitaux de Paris (Paris, France) and by the Institut Pasteur (Paris, France) (Postes d’accueil pour Praticiens Hospitaliers) and from a grant provided by INSERM, SFAR (Société Francaise d’Anesthésie et de Reanimation), and SRLF (Société de Réanimation de Langue Francaise) through the “Bourse de Recherche du Comité d’interface INSERM-SFAR-SRLF 2012”. F.J. is an employee of CNRS. %< avec comité de lecture %@ 2470-9468 %J Science Immunology %I American Association for the Advancement of Science (AAAS) %V 3 %N 22 %8 2018-04-13 %D 2018 %R 10.1126/sciimmunol.aan5997 %M 29654057 %Z Life Sciences [q-bio]/Immunology %Z Life Sciences [q-bio]/Immunology/AllergologyJournal articles %X Platelets are key regulators of vascular integrity; however, their role in anaphylaxis, a life-threatening systemic allergic reaction characterized by the loss of vascular integrity and vascular leakage, remains unknown. Anaphylaxis is a consequence of inappropriate cellular responses triggered by antibodies to generally harmless antigens, resulting in a massive mediator release and rapidly occurring organ dysfunction. Human platelets express receptors for immunoglobulin G (IgG) antibodies and can release potent mediators, yet their contribution to anaphylaxis has not been previously addressed in mouse models, probably because mice do not express IgG receptors on platelets. We investigated the contribution of platelets to IgG-dependent anaphylaxis in human IgG receptor-expressing mouse models and a cohort of patients suffering from drug-induced anaphylaxis. Platelet counts dropped immediately and markedly upon anaphylaxis induction only when they expressed the human IgG receptor FcγRIIA/CD32A. Platelet depletion attenuated anaphylaxis, whereas thrombocythemia substantially worsened its severity. FcγRIIA-expressing platelets were directly activated by IgG immune complexes in vivo and were sufficient to restore susceptibility to anaphylaxis in resistant mice. Serotonin released by activated platelets contributed to anaphylaxis severity. Data from a cohort of patients suffering from drug-induced anaphylaxis indicated that platelet activation was associated with anaphylaxis severity and was accompanied by a reduction in circulating platelet numbers. Our findings identify platelets as critical players in IgG-dependent anaphylaxis and provide a rationale for the design of platelet-targeting strategies to attenuate the severity of anaphylactic reactions. %G English %Z NASA study group : Vanessa Granger (UF Auto-immunité et Hypersensibilités, Hôpital Bichat, APHP, Paris, France; UMR996 - Inflammation, Chemokines et Immunopathology -, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France); Philippe Montravers (Département d’anesthésie-réanimation, Hôpital Bichat, AP-HP, Paris, France); Michel Aubier & Caroline Sauvan (Service de pneumologie et d’allergologie, Hôpital Bichat, AP-HP, Paris, France); Marc Fischler & Julie Bresson (Département d’anesthésie-réanimation, Hôpital Foch, Suresnes, France); Catherine Paugam-Burtz & Skander Necib (Département d’anesthésie-réanimation, Hôpital Beaujon, AP-HP, Clichy, France); Alexandre Mebazaa & Matthieu Le Dorze (Département d’anesthésie-réanimation, Hôpital Lariboisière, AP-HP, Paris, France); Laurent Jacob & Carole Chahine (Département d’anesthésie-réanimation, Hôpital Saint Louis, AP-HP, Paris, France); Hawa Keita-Meyer & Valentina Faitot (Département d’anesthésie-réanimation, Hôpital Louis Mourier, AP-HP, Colombes, France); Olivier Langeron & Sabrine Roche (Département d’anesthésie-réanimation, Hôpital Pitié Salpêtrière, AP-HP, Paris, France); Bernard Cholley & Jean Manz (Département d’anesthésie-réanimation, Hôpital Européen Georges Pompidou, AP-HP, Paris, France). %2 https://pasteur.hal.science/pasteur-01928557/document %2 https://pasteur.hal.science/pasteur-01928557/file/HAL%20Beutier%20et%20al%20Science%20Immunol%20revision%20format%20no%20marks%20vf.pdf %L pasteur-01928557 %U https://pasteur.hal.science/pasteur-01928557 %~ PASTEUR %~ UNIV-PARIS7 %~ UNIV-PSUD %~ APHP %~ UNIV-STRASBG %~ OPENAIRE %~ USPC %~ INSERM-SACLAY %~ UNIV-PARIS-SACLAY %~ UNIV-PSUD-SACLAY %~ SITE-ALSACE %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ SU-MED %~ UNIV-PARIS %~ UP-SANTE %~ SU-TI %~ ANR %~ ALLIANCE-SU %~ ANTIBODIES-THERAPY-PATHOLOGY %~ U1222