The central role of phosphatidylserine in the phagocytosis of apoptotic thymocytes

Apoptotic thymocytes inactivate the aminophospholipid translocase, which transports phosphatidylserine (PS) to the inner leaflet of the plasma membrane, and activate the scramblase, which randomizes phospholipids across the membrane and brings PS to the cell surface. Although different macrophages use at least two different systems to recognize and engulf apoptotic thymocytes, both systems recognize PS on the apoptotic target. Thymocytes treated with Ca2+ and ionophore to inactivate the translocase and activate the scramblase immediately expose PS on their surface and are immediately recognized and phagocytosed. These targets, on which PS has been artificially exposed, are recognized by the PS exposed on their surface. However, they apparently also engage the vitronectic receptor, a lectin-like receptor and CD14. All of these receptors are implicated in the phagocytosis of apoptotic thymocytes, suggesting that loss of asymmetry and/or exposure of PS is sufficient to generate the ligands recognized by those receptors. The role of PS is not confined to the target cell surface, however. PS is constitutively exposed on the Surface of macrophages and is as necessary for apoptotic cell engulfment as is recognition of PS on the target cell surface.