Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions

House dust mite (HDM) allergens are important factors in the increasing pre valence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 fr om fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruptio n of intercellular tight junctions (TJs), which are the principal component s of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occlud in. Cleavage was attenuated by antipain, but not by inhibitors of serine, a spartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ a dhesion protein claudin-1. TJ breakdown nonspecifically increased epithelia l permeability, allowing Der p 1 to cross the epithelial barrier. Thus, tra nsepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental protei nases may be the initial step in the development of asthma to a variety of allergens.