Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2468-2477 |
Number of pages | 10 |
Journal | European Journal of Immunology |
Volume | 44 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2014 |
Externally published | Yes |
Keywords
- Anaphylaxis
- ASGM1
- Basophil
- PAF
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology