A receptor for phosphatidylserine-specific clearance of apoptotic cells.
cytosis 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.
Fadok
V A
VA
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. fadokv@njc.org
Bratton
D L
DL
Rose
D M
DM
Pearson
A
A
Ezekewitz
R A
RA
Henson
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D005434:Flow Cytometry; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D019169:Jurkat Cells; D008081:Liposomes; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000911:Antibodies, Monoclonal; D008081:Liposomes; D010718:Phosphatidylserines; C498708:Ptdsr protein, mouse; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; C408123:phosphatidylserine receptor; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases