Engulfment of Apoptotic Cells and Its Physiological Roles

Abstract During development of animals, many cells undergo programmed cell death via apoptosis. In adult, senescent cells also undergo apoptosis and are replaced by newly generated cells. Apoptotic dying cells display an “eat‐me” signal(s) on their surface, and are recognized by macrophages and immature dendritic cells for engulfment. Phosphatidylserine, which is exposed on the cell surface in a caspase‐dependent manner, is the most likely candidate for the “eat‐me” signal. Phagocytes recognize phosphatidylserine through specific receptors or via bridging molecules that link them with the apoptotic cells. Phagocytes engulf the apoptotic cells in a Rac1‐dependent manner probably through specific portals. When apoptotic cells are not engulfed efficiently, they undergo secondary necrosis and release their cellular contents, which leads to local inflammation, production of autoantibodies, and SLE (systemic lupus erythematosus)‐type autoimmune diseases. Key concepts: Apoptotic cells are swiftly removed by phagocytes. Phosphatidylserine on apoptotic cells plays an important role as an “eat‐me” signal. Phosphatidylserine is recognized by both soluble molecules and surface receptors. The engulfment of apoptotic cells leads to an anti‐inflammatory response by the immune system. The inefficient removal of apoptotic cells leads to autoimmune diseases.