The airway epithelium forms a highly regulated physical barrier that normally prevents invasion of inhaled pathogens and allergens from the airway lumen. Beyond being a simple physical barrier, the airway epithelium is now known to be a prominent regulator of the immune response to environmental triggers. Epithelial barrier function is maintained by apposed cell-cell contacts consisting of tight junctions (TJs), gap junctions, adherens junctions, and desmosomes.

As far back as the early 1990s, ultrastructure studies demonstrated that the airway epithelium of the asthmatic patient has fewer intercellular adhesion junction complexes compared with that of the nonasthmatic patient, but the molecular mechanisms underlying these structural differences were not described. Recent studies have now identified that the asthmatic epithelium displays reduced and altered expression of the adhesion proteins E-cadherin and zonula occludens 1 (ZO-1). This phenomenon is not only confined to the lower airways because disrupted desmosome formation has also been shown in nasal polyps from asthmatic children. The proposed mechanism for this epithelial barrier damage was originally thought to occur because of downregulation of junctional proteins indirectly through inflammatory mediator release or directly through cleavage by allergens.

The presumed consequences of this disrupted epithelial barrier function would be increased access of inhaled allergens to antigen-presenting cells in the submucosa and spasmogenic agonists reaching the smooth muscle.

Authors : Darryl A. Knight, Stephen M. Stick, Tillie-Louise Hackett
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