Barrier function of airway tract epithelium

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

The major players that contribute to the mucociliary function of airway epithelium are mucus and cilia. While the mucus traps inhaled pathogens and other particulate material, coordinated beating of cilia sweeps the trapped material away from the lungs toward the pharynx. 35 The efficient transport of mucus is dependent on the rate of ciliary beating as well as the hydration of mucus, which contributes to its viscoelastic properties. 36, 37 In general, more hydrated mucus is cleared more efficiently from the lungs. The airway mucus contains more than 200 proteins, and is secreted by both goblet cells and submucosal glands. The main component of airway mucus are mucins, which are high molecular weight glycoproteins that cross link to form the structural framework of the mucus barrier. 38, 39 At least 12 mucins are detected in human lungs. Of these, MUC5AC and MUC5B are the predominant mucins in normal airways. 40 MUC5AC is mainly produced by goblet cells, while MUC5B is predominantly produced by submucosal glands. 41, 42 In healthy individuals, circadian rhythms regulate normal mucus secretion, principally through the vagal nerve. However in patients with inflammatory airway diseases, mucus hypersecretion from metaplastic and hyperplastic goblet cells contributes to obstruction of airways. 43 Various inflammatory mediators, such as tumor necrosis factor -α, IL-1β, IL-13, IL-17, neutrophil elastase, growth factors such as EGF and TGF, and environmental factors such as cigarette smoke, allergens and microbial pathogens Goblet cells have electron lucent granules which contain acidic mucin glycoproteins in the apical region of cytoplasm, and contain a condensed nucleus on the basal side giving the cells a unique shape. In normal conductive airways the ratio of goblet cell to ciliated cells is approximately 1:5 and this ratio increases under the conditions of chronic airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. The goblet cells secrete high molecular weight mucin glycoproteins into the airway lumen, which trap and remove foreign particles, thus protecting the epithelial surface. Mucin secretion must be tightly regulated for normal functioning, as overproduction can block the airway and impair proper mucociliary clearance.