title: Human FcγRIIA induces anaphylactic and allergic reactions.
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.
authors.affiliation: Institut Pasteur, Département d'Immunologie, Unité d'Allergologie Moléculaire et Cellulaire, Paris, France.
authors.forename: Friederike
authors.initials: F
authors.lastname: Jönsson
authors.forename: David A
authors.initials: DA
authors.lastname: Mancardi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kita
authors.forename: Bruno
authors.initials: B
authors.lastname: Iannascoli
authors.forename: Huot
authors.initials: H
authors.lastname: Khun
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schwartz
authors.forename: Marc
authors.initials: M
authors.lastname: Daëron
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010323:Passive Cutaneous Anaphylaxis; D017452:Receptors, IgG / Q000502:physiology*; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology*
chemical_list: C080568:Fc gamma receptor IIA; D017452:Receptors, IgG