A receptor for phosphatidylserine-specific clearance of apoptotic cells

Valerie A. Fadok (), Donna L. Bratton, David M. Rose, Alan Pearson, R. Alan B. Ezekewitz and Peter M. Henson
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Valerie A. Fadok: National Jewish Medical and Research Center
Donna L. Bratton: National Jewish Medical and Research Center
David M. Rose: National Jewish Medical and Research Center
Alan Pearson: Massachusetts General Hospital
R. Alan B. Ezekewitz: Massachusetts General Hospital
Peter M. Henson: National Jewish Medical and Research Center

Nature, 2000, vol. 405, issue 6782, 85-90

Abstract: Abstract The culmination of apoptosis in vivo is phagocytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally1,2,3,4. 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 recognized1,5,6,7,8,9,10. 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.

Date: 2000
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DOI: 10.1038/35011084

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