Document Detail

Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells.
MedLine Citation:
PMID:  15004195     Owner:  NLM     Status:  MEDLINE    
A major function of macrophages is to engulf apoptotic cells to prevent them from releasing noxious materials as they die. Milk fat globule-EGF-factor 8 (MFG-E8) is a glycoprotein secreted by activated macrophages that works as a bridge between apoptotic cells and phagocytes by specifically recognizing phosphatidylserine exposed on apoptotic cells. In this study, we found that developmental endothelial locus-1 (Del-1), originally identified as an embryonic endothelial cell protein that binds alphavbeta3 integrin, is structurally and functionally homologous to MFG-E8. That is, both consist of a signal sequence, two epidermal growth factor domains and two factor VIII-homologous domains (C1 and C2). Del-1 bound to the apoptotic cells by recognizing phosphatidylserine via the factor VIII-homologous domains with an affinity similar to that of MFG-E8. The phagocytic activity of NIH 3T3 cells against apoptotic cells was enhanced by Del-1 through an interaction between the epidermal growth factor domain in Del-1 and alphavbeta3 integrin expressed in the NIH 3T3 cells. Screening of primary macrophages and macrophage cell lines for the expression of MFG-E8 and Del-1 indicated that MFG-E8 and Del-1 are expressed in different sets of macrophages. These results suggest the existence of macrophage subsets that use MFG-E8 or Del-1 differently to engulf apoptotic cells.
Rikinari Hanayama; Masato Tanaka; Keiko Miwa; Shigekazu Nagata
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  172     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-08     Completed Date:  2004-07-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3876-82     Citation Subset:  AIM; IM    
Department of Genetics, Osaka University Medical School, Osaka, Japan.
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MeSH Terms
Adjuvants, Immunologic / biosynthesis,  metabolism,  physiology
Amino Acid Sequence
Antigens, Surface / biosynthesis,  metabolism,  physiology
Apoptosis* / immunology
Carrier Proteins / biosynthesis*,  metabolism,  physiology
Cell Line, Tumor
Cells, Cultured
Leukemia P388
Macrophages / metabolism*
Mice, Inbred C57BL
Mice, Transgenic
Milk Proteins / biosynthesis,  metabolism
Molecular Sequence Data
NIH 3T3 Cells
Phagocytosis* / immunology
Phosphatidylserines / metabolism
Protein Binding / immunology
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antigens, Surface; 0/Carrier Proteins; 0/Edil3 protein, mouse; 0/Mfge8 protein, mouse; 0/Milk Proteins; 0/Phosphatidylserines

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