Abstract
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.
- © 2011 ERS
