Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin-E-mediated systemic anaphylaxis.
Anaphylaxis is an acute, severe, and potentially fatal systemic allergic reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been associated with anaphylaxis, but an alternative pathway mediated by IgG has been suggested to be more important in the elicitation of anaphylaxis. Here, we showed that basophils, the least common blood cells, were dispensable for IgE-mediated anaphylaxis but played a critical role in IgG-mediated, passive and active systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes, basophils released platelet-activating factor (PAF), leading to increased vascular permeability. These results highlight a pivotal role for basophils in vivo and contrast two major, distinct pathways leading to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other "classical" pathway mediated by mast cells, IgE, and histamine.
Tsujimura
Yusuke
Y
Department of Immune Regulation and Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
Obata
Kazushige
K
Mukai
Kaori
K
Shindou
Hideo
H
Yoshida
Masayuki
M
Nishikado
Hideto
H
Kawano
Yohei
Y
Minegishi
Yoshiyuki
Y
Shimizu
Takao
T
Karasuyama
Hajime
H
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007073:Immunoglobulin E / Q000502:physiology*; D007074:Immunoglobulin G / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010972:Platelet Activating Factor / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
D000485:Allergens; D007074:Immunoglobulin G; D010972:Platelet Activating Factor; D017452:Receptors, IgG; D007073:Immunoglobulin E; D010047:Ovalbumin