1. Human FcγRIIA induces anaphylactic and allergic reactions
- Author
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Nico van Rooijen, Friederike Jönsson, Lawrence B. Schwartz, Takao Shimizu, Wei Zhao, Marc Daëron, David A. Mancardi, Yoshihiro Kita, Bruno Iannascoli, Pierre Bruhns, Huot Khun, Allergologie Moléculaire et Cellulaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virginia Commonwealth University (VCU), The University of Tokyo (UTokyo), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Department of Molecular Cell Biology [Amsterdam UMC], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU)-Vrije Universiteit Amsterdam [Amsterdam] (VU), This work was supported by the Institut Pasteur, Inserm, the Agence Nationale de la Recherche (ANR, grant GENOPAT-09-GENO-014-01), the Société Française d'Allergologie (SFA, Soutien de la recherche en allergologie 2010), and the Balsan company. F.J. is a recipient of a fellowship from the Fondation pour la Recherche Médicale (FRM). D.A.M. is a recipient of a fellowship from the Institut Pasteur (Bourse Roux). W.Z. and L.B.S. were funded in part by U19AI077435 from the National Institutes of Health., ANR-09-GENO-0014,InflammAbs,Contrôle de l'inflammation par les RFc humains dans des modèles murins d'allergie et d'autoimmunité.(2009), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Molecular cell biology and Immunology, and CCA - Immuno-pathogenesis
- Subjects
MESH: Inflammation ,Allergy ,Respiratory System ,mast cells ,airway inflammation ,MESH: Neutrophils ,Immunoglobulin E ,MESH: Mice, Knockout ,Biochemistry ,0302 clinical medicine ,neutrophils ,MESH: Animals ,[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology ,Receptor ,Cells, Cultured ,MESH: Respiratory System ,Mice, Knockout ,0303 health sciences ,biology ,Passive Cutaneous Anaphylaxis ,Airway inflammation ,MESH: Mast Cells ,Hematology ,immunoglobulin e ,macrophages ,3. Good health ,immunoglobulin g ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,hypersensitivity ,monocytes ,MESH: Passive Cutaneous Anaphylaxis ,MESH: Cells, Cultured ,mice ,MESH: Mice, Transgenic ,MESH: Hypersensitivity ,Immunology ,Mice, Transgenic ,MESH: Receptors, IgG ,03 medical and health sciences ,MESH: Eosinophils ,MESH: Mice, Inbred C57BL ,In vivo ,anaphylaxis ,medicine ,Animals ,Humans ,MESH: Mice ,030304 developmental biology ,Inflammation ,MESH: Humans ,Passive anaphylaxis ,business.industry ,Receptors, IgG ,Anaphylactic reactions ,Cell Biology ,medicine.disease ,Eosinophils ,Mice, Inbred C57BL ,biology.protein ,business ,030215 immunology - Abstract
IgE and IgE receptors (FcϵRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcϵRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils, and eosinophils do not express FcγRIIIA or FcγRIV, but FcγRIIA. We therefore investigated the possible role of FcγRIIA in allergy by generating novel FcγRIIA-transgenic mice, in which various models of allergic reactions induced by IgG could be studied. In mice, FcγRIIA was sufficient to trigger active and passive anaphylaxis, and airway inflammation in vivo. Blocking FcγRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcγRIIA-dependent passive cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be responsible for FcγRIIA-dependent passive systemic anaphylaxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators after FcγRIIA engagement. IgG and FcγRIIA may therefore contribute to allergic and anaphylactic reactions in humans.
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- 2012