RRC ID 67483
Author Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S.
Title Identification of a factor that links apoptotic cells to phagocytes.
Journal Nature
Abstract Apoptotic cells are rapidly engulfed by phagocytes to prevent the release of potentially noxious or immunogenic intracellular materials from the dying cells, thereby preserving the integrity and function of the surrounding tissue. Phagocytes engulf apoptotic but not healthy cells, indicating that the apoptotic cells present a signal to the phagocytes, and the phagocytes recognize the signal using a specific receptor. Here, we report a factor that links apoptotic cells to phagocytes. We found that milk fat globule-EGF-factor 8 (MFG-E8), a secreted glycoprotein, was produced by thioglycollate-elicited macrophages. MFG-E8 specifically bound to apoptotic cells by recognizing aminophospholipids such as phosphatidylserine. MFG-E8, when engaged by phospholipids, bound to cells via its RGD (arginine-glycine-aspartate) motif--it bound particularly strongly to cells expressing alpha(v)beta(3) integrin. The NIH3T3 cell transformants that expressed a high level of alpha(v)beta(3) integrin were found to engulf apoptotic cells when MFG-E8 was added. MFG-E8 carrying a point mutation in the RGD motif behaved as a dominant-negative form, and inhibited the phagocytosis of apoptotic cells by peritoneal macrophages in vitro and in vivo. These results indicate that MFG-E8 secreted from activated macrophages binds to apoptotic cells, and brings them to phagocytes for engulfment.
Volume 417(6885)
Pages 182-7
Published 2002-5-9
DOI 10.1038/417182a
PII 417182a
PMID 12000961
MeSH 3T3 Cells Animals Antibodies, Monoclonal / immunology Antigens, Surface* Apoptosis* Cell Adhesion Cell Line Cricetinae Cricetulus Endocytosis / drug effects Enzyme-Linked Immunosorbent Assay Flow Cytometry Macrophages, Peritoneal / cytology Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / physiology* Membrane Glycoproteins / chemistry Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Mice Milk Proteins* Oligopeptides / metabolism Phagocytes / cytology Phagocytes / drug effects Phagocytes / physiology* Phosphatidylserines / metabolism Receptors, Vitronectin / metabolism Thioglycolates / pharmacology Thymus Gland / cytology Thymus Gland / drug effects
IF 42.779
DNA material pEF-MFG-E8/L/Flag (RDB18989) pEF-MFG-E8/S/Flag (RDB18990) pEF-MFG-E8/C1C2/Flag (RDB18991) pEF-MFG-E8/C2/Flag (RDB18992) pEF-MFG-E8/E1E2PT/Flag (RDB18993) pEF-MFG-E8/D89E/Flag (RDB18994)