Apoptosis in lung injury and disease

Pulmonary cell death may contribute significantly to acute and chronic lung injuries caused by various adverse environmental agents. Pulmonary cells may die by necrosis, apoptosis, and other forms of regulated cell death. Apoptosis exerts a homeostatic function in lung defense and development, through the removal of dysfunctional cells and by regulating cellular proliferation. Lung cell apoptosis can occur as a response to oxidative stress, mechanical ventilation, ischemia/reperfusion, cigarette smoke exposure, and other forms of acute and chronic lung injuries. The role of apoptosis in the pathogenesis of chronic lung disease remains controversial. Apoptosis may act as an adaptive process, by removing dysfunctional cells, limiting inflammation in damaged tissue, and preventing cell proliferation. On the other hand, excessive apoptosis may contribute to the depletion of critical cell populations, resulting in loss of function, as in emphysema, or in undesirable cell proliferation, as in fibrosis and pulmonary hypertension. An understanding of the cell-type-specific regulation and function of apoptosis in the lung may facilitate the development of therapeutic strategies for the treatment of lung pathologies. This chapter reviews the current evidence for the regulation and function of apoptosis in specific lung diseases, with an emphasis on chronic obstructive lung disease and acute respiratory distress syndrome.