Pneumologie 2012; 66 - P1_008
DOI: 10.1055/s-0032-1329799

House dust mite-induced ATP release plays a role in the innate immunological response and barrier dysfunction of airway epithelium

S Post 1, M Nawijn 1, A van Oosterhout 1, I Heijink 1
  • 1Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

Background: House dust mite (HDM) affects both the barrier and the innate immune functions of the airway epithelium. The release of ATP upon HDM administration has been shown to be critically required for allergic sensitization, airway remodeling and eosinophilic inflammation in a mouse model.

Objective: We sought to determine the role of ATP release in the HDM-induced altered barrier function and innate immune responses of airway epithelium.

Methods: We investigated the effect of HDM on accumulation of intracellular Ca2+ levels ([Ca2+]i) (Ca2+ influx assay), barrier function (ECIS) and CCL20 release (ELISA) in human bronchial epithelial cells. Involvement of ATP-dependent activation of purinergic receptors and downstream Ca2+ signaling was determined using the calcium chelator BAPTA-AM, the purinergic receptor and calpain inhibitors and the ATP hydrolyzing agent apyrase. We additionally examined barrier function and CCL20 release in primary bronchial epithelial cells (PBECs) from healthy subjects and asthma patients.

Results: HDM exposure resulted in prolonged [Ca2+]i accumulation in airway epithelium, and that Ca2+ release through activation of the purinergic receptors is involved in HDM-induced barrier dysfunction and delocalization of E-cadherin and occludin. Furthermore, the increase in [Ca2+]i was involved in HDM-induced CCL20 secretion in bronchial epithelial cells. Moreover, experiments with PBECs revealed an aggravated decrease in barrier function as well as a stronger induction of CCL20 secretion in asthmatic compared to healthy PBECs after HDM exposure.

Conclusion: Our data show for the first time that Ca2+ signaling may play a crucial role in barrier dysfunction and the immunological response of airway epithelium upon HDM exposure.

This study is sponsored by the Dutch Asthma Foundation (AF 3.2.07.019)