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A receptor for phosphatidylserine-specific clearance of apoptotic cells
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Journal Article
A receptor for phosphatidylserine-specific clearance of apoptotic cells
2000
Overview
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
1
,
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 recognized
1
,
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.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Animals
/ Antibodies, Monoclonal - immunology
/ Biological and medical sciences
/ Cells
/ Cloning
/ Fundamental and applied biological sciences. Psychology
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Jumonji Domain-Containing Histone Demethylases
/ letter
/ Mice
/ Molecular and cellular biology
/ Phosphatidylserines - metabolism
/ Receptors, Cell Surface - genetics
/ Receptors, Cell Surface - immunology
/ Receptors, Cell Surface - physiology
/ Science
