Barrier function of airway tract epithelium

Ganesan, Shyamala; Comstock, Adam T; Sajjan, Uma S

The three barrier functions of airway epithelial tract, mucociliary clearance, intercellular apical junctional complexes and antimicrobial products of airway function together to effectively clear inhaled pathogens, allergens and pollutants from the lungs. The intercellular apical junctional complex not only regulates paracellular permeability, but also separates proteins of basolateral surface from apical surface and promotes normal differentiation of airway tract epithelial cells. This is critical for regulation of secretion of mucus and antimicrobial proteins and peptides, and also for maintenance of viscosity and depth of ASL, in which cilia beat. Barrier function of airway tract epithelium is compromised in patients with chronic airways disease due to repetitive injury and abnormal repair leading to airway remodeling. Understanding the molecular mechanisms of airway epithelial repair under normal and chronic disease conditions is necessary to develop therapies to prevent airway remodeling and promote normal epithelial repair. However, the field of airway epithelial repair is in its infancy, because airway epithelium is complex and comprises several cell types and the cells show remarkable however, allergens are thought to be primary stimulus responsible for airway remodeling. It was demonstrated that proteases present in the allergens disrupt not only tight junctions but also adherens junctions 129, 130 and this could lead to both EGFR activation and Wnt/β-catenin signaling ultimately resulting in development of goblet cell metaplasia/hyperplasia.