IgG-mediated anaphylaxis via Fc gamma receptor in CD40-deficient mice.
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.
Wakayama
H
H
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hasegawa
Y
Y
Kawabe
T
T
Saito
H
H
Kikutani
H
H
Shimokata
K
K
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*
D019013:CD40 Antigens; D007074:Immunoglobulin G; D017452:Receptors, IgG