LSC 2011 Abstract: Combined nasal exposure to sodium hypochlorite and ovalbumin induces airway hyperreactivity in mice through activation of the TRPA1 channel and mast cells

Background: Some epidemiologic studies have indicated that attendance to chlorinated swimming pools is associated with bronchial hyperreactivity, allergies and asthma. Aim: To investigate the effects of NaClO, the main pool disinfectant, on allergic sensitization and airway responses in mice. Methods: Male BALB/c mice received 1 to 7 nasal instillations of ovalbumin (OVA, 1%) on alternate days 10 min after instillation of NaClO (3 ppm active chlorine) or water. 48h after 1, 3, 5 and 7 instillations, we measured airway reactivity to methacholine (Flexivent), cellular inflammation in broncho-alveolar lavage (BAL), lung cytokines, and serum OVA-specific IgE. Later, methacholine reactivity 48 h after a single combined NaClO-OVA exposure was assessed in mice pretreated with the neurokinin1 receptor antagonist RP67580, in knock-out mice deficient in the transient receptor potential (TRP) channel A1 (TRPA1 -/- ) or V1 (TRPV1 -/- ) and in mast cell deficient mice ( Kit W-sh /Kit W-sh ). Results: Combined nasal NaClO-OVA exposure induced airway hyperreactivity (AHR) to methacholine in the absence of airway inflammation and OVA specific IgEs. AHR was already induced after a single combined exposure to NaClO-OVA and it was not observed after either OVA or NaClO alone. The AHR response was reduced after pretreatment with RP67580. NaClO-OVA induced AHR in TRPV1 -/- mice, but not in TRPA1 -/- mice and mast cell deficient mice. Conclusion: Combined nasal NaClO-OVA exposure induces AHR in the absence of allergic inflammation. This effect appears to involve TRPA1, mast cells and release of substance P, suggesting a neuro-immune interaction.