Clearance: the last and often forgotten stage of apoptosis.

Engulfment by a phagocyte is the final common event in the life of most apoptotic cells. Phagocytosis of apoptotic bodies prior to their lysis prevents the release of potentially toxic or immunogenic intracellular contents and activates an anti-inflammatory response, at least in macrophages. We are beginning to understand the mechanisms by which macrophages and other phagocytes recognize apoptotic cells in vitro, but we are a long way from determining their relative importance in vivo. The involuting mammary gland undergoes massive cell loss by apoptosis. The dying alveolar epithelial cells can be shed into the lumen or can be phagocytosed by macrophages and viable epithelial cells. Yet we know virtually nothing about the mechanisms mediating recognition and uptake in the mammary gland. It is likely that clearance of apoptotic cells is critical to normal remodeling of the gland in preparation for the next wave of lactation. The mammary gland, therefore, provides an ideal organ in which to study the mechanisms and consequences of apoptotic cell clearance in vivo.