Introduction: Allergic asthma is mainly caused by exposure to aeroallergens like house dust mite (HDM), when transepithelial delivery is facilitated by disruption of the epithelial barrier. Objective: We aimed to gain more insight in which biochemical property of HDM is critical for the disruption of barrier function and initiates an inflammatory response. Methods: HDM extracts with different biochemical properties were analyzed for their effects on airway/bronchial epithelial barrier function by measuring changes in transepithelial resistance and immunostaining of the junctional proteins ZO-1, occludin and E-cadherin. Furthermore, we examined the induction of a pro-inflammatory phenotype of human bronchial epithelium by these HDM extracts, as well as the epithelial remodeling and airway inflammation in vivo in a mouse model. Results: We found that the different HDM extracts induced divergent responses. Importantly, the extract with lowest serine protease activity induced the most pronounced effects on barrier function in vitro , and induced an increased production of the pro-inflammatory chemokine CCL20. Remarkably, the same HDM extract induced HDM-specific IgE, a profound epithelial E-cadherin delocalization, goblet cell hyperplasia, cellular inflammation and increased levels of CCL17 and IL-5 in vivo . Conclusion: Together, these results indicate that the disruption in epithelium barrier function is independent of serine protease activity, and is essential for allergic sensitization and airway remodeling in vivo .
Post et al. (Thu,) studied this question.