Cells dying by apoptosis are swiftly ingested by macrophages before they rupture and release injurious and immunogenic contents into the surrounding tissue, and thus clearance of apoptotic cells by macrophages is important in maintaining tissue homeostasis and in tissue remodeling. In a series of studies, we have found a novel mechanism of phagocytic recognition of apoptotic cells that involves cell-surface carbohydrate chains of the apoptotic cells. The outlines of the phagocytic recognition of apoptotic cells including the carbohydrate-mediated novel mechanism are as follows.
1. At an early stage of apoptosis of lymphocytes, glycoprotein molecules (e.g., CD43) on apoptotic cell membrane localize to one pole of the cell and form a large cluster (cap) of the glycoprotein molecules. Macrophages recognize the apoptotic cells at this stage through the carbohydrate chains of the glycoprotein cluster.
2. The glycoprotein cluster gradually disappears from the cell surface in a few hours probably due to proteolytic degradation. Accordingly, the apoptotic cells become less susceptible to the macrophage recognition.
3. In contrast, phosphatidylserine (PS) exposure becomes observable around this time and increases thereafter. Susceptibility of the apoptotic cells to macrophage recognition increases again as PS exposure increases.
Furthermore, the macrophage receptor involved in the carbohydrate-mediated recognition of the early apoptotic cells was identified to be a 110 kDa protein that is known to be usually present in nuclei.