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

Hox, Valérie;Vanoirbeek, Jeroen A;Alpizar, Yeranddy A;Voedisch, Sabrina;Hellings, Peter W;et.al.
(2013) American Journal of Respiratory and Critical Care Medicine — Vol. 187, p. 486-493 (2013)

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Authors
  • Hox, Valérieorcid-logoUCLouvain
    Author
  • Vanoirbeek, Jeroen A
    Author
  • Alpizar, Yeranddy A
    Author
  • Voedisch, Sabrina
    Author
  • Hellings, Peter W
    Author
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Abstract
RATIONALE: 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. OBJECTIVES: To investigate the mechanisms of ClO(-)-OVA-induced nonallergic AHR. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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
Affiliations
  • KULUniversity Hospitals Leuven

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Hox, V., Vanoirbeek, J. A., Alpizar, Y. A., Voedisch, S., Callebaut, I., Bobic, S., Sharify, A., De Vooght, V., Van Gerven, L., Devos, F., Liston, A., Voets, T., Vennekens, R., Bullens, D. M. A., De Vries, A., Hoet, P., Braun, A., Ceuppens, J. L., Talavera, K., et al. (2013). Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice. American Journal of Respiratory and Critical Care Medicine, 187, 486-493. https://doi.org/10.1164/rccm.201208-1358OC (Original work published 2013)