A receptor for phosphatidylserine-specific clearance of apoptotic cells

The culmination of apoptosis in vivo is phagocytosis of cellular corpses. D uring apoptosis, the asymmetry of plasma membrane phospholipids is lost, wh ich exposes phosphatidylserine externally(1-4). The phagocytosis of apoptot ic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogues, but not by other anionic phospholipids, suggesting th at phosphatidylserine is specifically recognized(1,5-10). Using phage displ ay, we have cloned a gene that appears to recognize phosphatidylserine on a poptotic cells. Here we show that this gene, when transfected into B and T lymphocytes, enables them to recognize and engulf apoptotic cells in a phos phatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macroph ages, fibroblasts and epithelial cells; this antibody, like phosphatidylser ine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrop hages, induced an anti-inflammatory state. This candidate phosphatidylserin e receptor is highly homologous to genes of unknown function in Caenorhabdi tis elegans and Drosophila melanogaster, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highl y conserved throughout phylogeny.