Examination of the role of TRPM8 in human mast cell activation and its relevance to the etiology of cold-induced uricaria

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	IMMUNO/INFLAM-18

Authors

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

Abstract

Mast cells are considered the primary initiators of allergic diseases as a consequence of the release of multiple inflammatory mediators on activation. Although predominately activated through antigen-mediated aggregation of IgE-occupied-FcεRI, they can also be induced to release mediators by other receptors and environmental stimuli. Based on studies conducted in the RBL-2H3 rodent mast cell line, the transient receptor potential melastatin 8 (TRPM8) cation channel has been implicated in the activation of mast cells in response to cold and, by inference, the development of urticaria. Here we investigated the expression and role of TRPM8 receptor, in both human and mouse non-transformed cells, with the aim of exploring the potential link between TRPM8 and the pathology of cold urticaria in humans. Although expressed in mouse mast cells, we found no evidence of TRPM8 expression in human mast cells nor functional mutations in trpm8 in cold urticaria patients. Furthermore, neither mouse nor human mast cells degranulated in response to cold challenge or TRPM8 agonists and mast cell reactivity was unaffected in trpm8-/- mice. From these data, we conclude that TRPM8 is unlikely to directly regulate mast cell activation in cold urticaria. Thus alternative mechanisms likely exist for the pathogenesis of this disease.

back to top