Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice.

Authors: Valérie Hox, Jeroen A Vanoirbeek, Yeranddy A Alpizar, Sabrina Voedisch, Ina Callebaut, Sonja Bobic, Ali Sharify, Vanessa De Vooght, Laura Van Gerven, Fien Devos, Adrian Liston, Thomas Voets, Rudi Vennekens, Dominique M A Bullens, Annick de Vries, Peter Hoet, Armin Braun, Jan L Ceuppens, Karel Talavera, Benoit Nemery, Peter W Hellings

Journal, date & volume: Am. J. Respir. Crit. Care Med., 2013 Mar 1 , 187, 486-93

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23262517

Abstract
Airway hyperreactivity (AHR) is a key feature of bronchial asthma, and inhalation of irritants may facilitate development of nonallergic AHR. Swimmers exposed to hypochlorite (ClO(-))-containing water show a higher risk of developing AHR. We developed a mouse model in which instillation of ClO(-) before ovalbumin (OVA) induces AHR without bronchial inflammatory cells.To investigate the mechanisms of ClO(-)-OVA-induced nonallergic AHR.The involvement of the transient receptor potential ankyrin (TRPA)1 channel was checked in vivo by the use of TRPA1(-/-) mice and in vitro by Ca(2+) imaging experiments. The role of substance P (SP) was investigated by pretreating animals with the receptor antagonist RP67580, by replacing ClO(-) with SP in vivo, and by immunofluorescent staining of large airways of exposed mice. The role of mast cells was evaluated by exposing mast cell-deficient Kit(Wh)/Kit(Wsh) mice to ClO(-)-OVA with or without mast cell reconstitution.ClO(-)-OVA did not induce AHR in TRPA1(-/-) mice, and ClO(-) generates a Ca(2+) influx in TRPA1-transfected cells. Pretreatment with RP67580 reduces ClO(-)-OVA-induced AHR, although no increased SP expression was shown in the airways. SP-OVA exposure resulted in the same AHR as induced by ClO(-)-OVA. Kit(Wsh)/Kit(Wsh) mice did not develop AHR in response to ClO(-)-OVA unless they were reconstituted with bone marrow-derived mast cells.Induction of AHR by exposure to ClO(-)-OVA depends on a neuroimmune interaction that involves TRPA1-dependent stimulation of sensory neurons and mast cell activation.