House dust mite potentiates capsaicin‐evoked Ca 2+ transient in mouse pulmonary sensory neurons via protease‐activated receptor‐2

House dust mite (HDM) is the major source of allergen in house dust and has been suggested to be involved in the pathogenesis of asthma. In this study, we aimed to investigate whether HDM can modulate the sensitivity of pulmonary sensory neurons, and if so, to elucidate the underlying mechanism. Fura‐2 based ratio‐metric Ca 2+ imaging was carried out to determine the effect of HDM (Dermatophagoides pteronyssinus) extract on the capsaicin‐evoked Ca 2+ transient in mouse vagal pulmonary sensory neurons. Pretreatment with HDM (50 μg/ml, 5 min) significantly enhanced the Ca 2+ transient evoked by capsaicin (0.5 μM, 30 s) in these neurons isolated from wildtype (C57BL/6) mice. This potentiating effect of HDM was not affected by E64 (10 μM, 5 min), a selective cysteine protease inhibitor, but was completely prevented by AEBSF (50 μM, 5 min), a specific serine protease inhibitor. In addition, the potentiating effect of HDM on capsaicin‐evoked Ca 2+ transient was absent in the pulmonary sensory neurons isolated from protease‐activated receptor‐2 knockout mice. In summary, our results demonstrate that HDM, mainly through its serine protease activity, potentiates capsaicin‐evoked Ca 2+ transient in mouse pulmonary sensory neurons via the activation of protease‐activated receptor‐2. Funded by grants from AHA 0835320N, and NIH AI076714 and HL096914.