A receptor for phosphatidylserine-specific clearance of apoptotic cells

• Published in: Nature (London) Vol. 405; no. 6782; pp. 85 - 90
• Main Authors: Fadok, Valerie A, Bratton, Donna L, Rose, David M, Pearson, Alan, Ezekewitz, R. Alan B, Henson, Peter M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 04.05.2000; Nature Publishing Group
• Subjects: Ageing, cell death; Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Apoptosis; B-Lymphocytes - metabolism; Biological and medical sciences; Blotting, Western; Caenorhabditis elegans; Cell Line; Cell physiology; Cells; Cloning; Cloning, Molecular; Drosophila melanogaster; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Genes; Genes. Genome; Humans; Jumonji Domain-Containing Histone Demethylases; Jurkat Cells; Liposomes; Lymphocytes; Macrophages - immunology; Macrophages - metabolism; Macrophages - physiology; Membranes; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Molecules; Phagocytosis; phosphatidylserine; Phosphatidylserines - metabolism; Phylogeny; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Cell Surface - physiology; Sequence Homology, Amino Acid; T-Lymphocytes - metabolism; Transfection; Transforming Growth Factor beta - metabolism; Vertebrata; Mammalia; Gene; Mouse; Rodentia; Homology; Gene expression; Phosphatidylserine; Phagocytosis; Apoptosis; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35011084

The culmination of apoptosis in vivo is phagocytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally. The phagocytosis of apoptotic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogues, but not by other anionic phospholipids, suggesting that phosphatidylserine is specifically recognized. Using phage display, we have cloned a gene that appears to recognize phosphatidylserine on apoptotic cells. Here we show that this gene, when transfected into B and T lymphocytes, enables them to recognize and engulf apoptotic cells in a phosphatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macrophages, fibroblasts and epithelial cells; this antibody, like phosphatidylserine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrophages, induced an anti-inflammatory state. This candidate phosphatidylserine receptor is highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highly conserved throughout phylogeny.