Alterations in cell surface phosphatidylserine and sugar chains during apoptosis and their time-dependent role in phagocytosis by macrophages

Apoptotic cells are effectively ingested and removed by phagocytes. This process is dependent on specific recognition by phagocytes of ligands expressed exclusively on apoptotic cells. These ligands, cell surface molecules such as phosphatidylserine (PS), altered sugar chains, and the thrombospondin-binding domain, are expressed following the induction of apoptosis. However, they are not expressed simultaneously, and each factor seems to have a respective role in different phases of apoptosis. In this paper, we classified the apoptotic process into three phases (initial phase, metaphase, and later phase) according to cell viability, the expression of PS, and the change of sugar chains, and studied the role of individual molecules in the phagocytosis of apoptotic cells in each phase. We found that in the initial phase, characterized by an increase in PS expression but no decrease in cell viability, and metaphase, characterized by a decrease in cell viability and a change of cell surface sugar chains, PS, galactose, and the vitronectin receptor play important roles. In the later phase, when each factor is respectively constant, PS and galactose play important roles in phagocytosis, but the vitronectin receptor does not. We suggest that cell surface molecules respectively fulfill their role in the apoptotic process.