Basophil activation through ASGM1 stimulation triggers PAF release and anaphylaxis-like shock in mice.
Basophils have been shown to contribute to anaphylaxis through either an IgE-FcεRI-dependent pathway or an IgG-FcγR pathway. However, it remains largely unclear whether basophils can be activated to promote anaphylaxis via a non-FcR pathway as well. The glycolipid receptor ASGM1 (Asialoganglioside gangliotetraosylceramide), which has an exposed GalNAcβ1-4Gal moiety and serves as a receptor for pathogen associated molecular patterns such as flagellin, was recently found to be expressed on basophils. Here, we demonstrate that stimulation of basophils with anti-ASGM1 antibodies promotes platelet-activating factor (PAF) secretion in vitro and in vivo. Moreover, we found that ASGM1 stimulation triggers basophil- and PAF-dependent anaphylactic shock in pertussis toxin (PTX)-pretreated mice. Thus, ASGM1 has a crucial role in basophil activation and basophil-mediated anaphylaxis-like shock in mice, especially when the vascular permeability is increased by PTX treatment. Our findings describe a novel anaphylaxis-associated pathway that is antigen-, antibody-, and FcR-independent.
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Laboratory of Infection and Immunity, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Yan
Y
Yang
Daling
D
Li
Foad
F
Katirai
Bin
B
Zhang
Yong
Y
Xu
Ping
P
Xiong
Feili
F
Gong
Fang
F
Zheng
D000707:Anaphylaxis / Q000097:blood / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D002199:Capillary Permeability / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; C033639:glycolipid receptor; D007073:Immunoglobulin E
ASGM1; Anaphylaxis; Basophil; PAF