title: IgG-mediated anaphylaxis via Fc gamma receptor in CD40-deficient mice.
abstract: Anaphylaxis denotes an immediate hypersensitivity reaction to allergen, exclusively mediated by IgE antibodies. However, IgE antibodies do not explain all the syndromes that are encountered. We investigated potent IgG-mediated anaphylaxis in CD40-deficient mice that lack the immunoglobulin class switching for T cell-dependent antigens. Immunization with ovalbumin did not induce either humoral responses of IgG, IgA, and IgE, or systemic anaphylaxis in CD40-deficient mice. Although systemic anaphylaxis by active immunization was not observed in CD40-deficient mice, both passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis assessed by mouse blood pressure monitoring with cervical artery catheterization did take place when antigen-specific IgG was transferred and then antigen challenge given. Further, to investigate the inflammatory pathway of IgG-mediated immediate hypersensitivity reactions, we focused on the Fc gamma receptor (Fc gammaR) function. Pretreatment of the mice with the anti-Fc gammaRII/Fc gammaRIII MoAb clearly blocked the response of PCA and passive systemic anaphylaxis, suggesting that they were initiated through Fc gammaR. In conclusion, we directly demonstrate the IgG-mediated anaphylaxis and its triggering mechanism through Fc gammaR in in vivo conditions. In addition to IgE-mediated anaphylaxis, IgG-mediated anaphylaxis should be considered and the blocking of Fc gammaR would provide one of the therapeutic targets for the control of IgG-mediated hypersensitivity diseases.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Wakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Kawabe
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Kikutani
authors.forename: K
authors.initials: K
authors.lastname: Shimokata
mesh_terms: D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D007074:Immunoglobulin G; D017452:Receptors, IgG