The airway epithelium functions primarily as a barrier to foreign particles and as a modulator of inflammation. Apoptosis is induced in airway epithelial cells (AECs) by viral and bacterial infections, destruction of the cytoskeleton, or by exposure to toxins such as high oxygen and polycyclic hydrocarbons. Various growth factors and cytokines including TGF-beta, IFN-gamma, or the activators of the death receptors, TNF-alpha and FasL, also induce apoptosis in AECs. However, cell death is observed in maximally 15 of AECs after 24 h of treatment. Preincubation with IFN-gamma or a zinc deficiency increases the percentage of apoptotic AECs in response to TNF-alpha or FasL, suggesting that AECs have mechanisms to protect them from cell death. Apoptosis of AECs is a major mechanism in reducing cell numbers after hyperplastic changes in airway epithelia that may arise due to major injuries in response to LPS or allergen exposures. Resolution of hyperplastic changes or changes during prolonged exposure to an allergen is primarily regulated by the Bcl-2 family of proteins. Fas and FasL are both expressed in AECs, and their main function may be to control inflammation by inducing Fas-induced death in inflammatory cells without inducing apoptosis in neighboring cells. Furthermore, AECs engulf dying eosinophils to clear them by phagocytosis. Therefore, in the airway epithelium apoptosis serves three main roles: (1) to eliminate damaged cells; (2) to restore homeostasis following hyperplastic changes; and (3) to control inflammation, and thereby support the barrier and anti-inflammatory functions.
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