Science review: Apoptosis in acute lung injury

Apoptosis is a process of controlled cellular death whereby the activation of specific death-signaling pathways leads to deletion of cells from tissue. The importance of apoptosis resides in the fact that several steps involved in the modulation of apoptosis are susceptible to therapeutic intervention. In the present review we examine two important hypotheses that link apoptosis with the pathogenesis of acute lung injury in humans. The first of these, namely the 'neutrophilic hypothesis', suggests that during acute inflammation the cytokines granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor prolong the survival of neutrophils, and thus enhance neutrophilic inflammation. The second hypothesis, the 'epithelial hypothesis', suggests that epithelial injury in acute lung injury is associated with apoptotic death of alveolar epithelial cells triggered by soluble mediators such as soluble Fas ligand. We also review recent studies that suggest that the rate of clearance of apoptotic neutrophils may be associated with resolution of neutrophilic inflammation in the lungs, and data showing that phagocytosis of apoptotic neutrophils can induce an anti-inflammatory phenotype in activated alveolar macrophages.