Ceramide-CD300f interaction inhibits Mrgprb2-mediated mast cell activation and pseudo-allergic drug reactions in mice

Abstract

Abstract We have previously identified ceramide as a ligand for an inhibitory receptor CD300f (also called LMIR3) and demonstrated that ceramide-CD300f interaction inhibits IgE- and mast cell-dependent allergic responses. According to a recent report, basic secretagogues including inflammatory peptides and drugs associated with allergic-type reactions (c. g., compound 48/80, Ciprofloxacin, or Icatibant) activated connective tissue-type mast cells via Mrgprb2 in mice or via MRGPRX2 in human. To investigate a role of CD300f in pseudo-allergic reactions in mice, compound 48/80, Ciprofloxacin, or Icatibant together with Evans blue dye was intradermally injected into wild-type or CD300f-deficient mice. The results showed that CD300f deficiency enhanced vascular permeability in skin treated with basic secretagogues. Interestingly, ceramide-CD300f interaction inhibited compound 48/80-stimulated degranulation of peritoneal mast cells. Moreover, pretreatment with anti-ceramide antibody or ceramide vesicles enhanced or inhibited vascular permeability in compound 48/80-stimulated skin of wild-type mice. On the other hand, the same pretreatment failed to influence vascular permeability in compound 48/80-stimulated skin of CD300f-deficient mice. Thus, ceramide-CD300f interaction inhibits IgE-independent Mrgprb2-mediated pseudo-allergic reactions as well as IgE-dependent allergic reactions.