Delayed recovery from anaphylaxis in TRPC1-/- mice is driven by the elevated mast cell production of TNF-α

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	IMMUNO/INFLAM-5

Authors

• A Desai
• N Medic
• H Komarow
• MA Beaven
• AM Gilfillan
• DD Metcalfe

Abstract

Mast cell (MC) activation during the allergic reactions occurs mainly thought the high affinity receptor for IgE (FcεRI). We previously demonstrated that the RBL-2H3 mast cell line expresses transient receptor potential channel (TRPC)1, however it’s function and regulation in mast cells remained unknown. To explore a potential role of TRPC1 in mast cell activation, we examined antigen-mediated anaphylaxis in trpc1-/- and wild type mice, and antigen-mediated responses in MC derived from the bone marrow of these mice. In vivo studies revealed delayed recovery from passive systemic anaphylaxis in the trpc1-/- mice compared to wild type controls. However, this difference was negated by administration of an anti-TNF-α antibody two hours before induction of anaphylaxis. Contrary to expectations, mast cells derived from the bone marrow of the trpc1-/- mice had an exaggerated calcium signal in response to antigen, but little defect in degranulation. Furthermore, antigen-mediated TNF-α production was enhanced in these mice. These data thus provide evidence that, by negatively regulating mast cell TNF-α production, TRPC1 may promote recovery from the anaphylactic response.

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