| RRC ID |
67481
|
| Author |
Hanayama R, Tanaka M, Miwa K, Nagata S.
|
| Title |
Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells.
|
| Journal |
J Immunol
|
| Abstract |
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.
|
| Volume |
172(6)
|
| Pages |
3876-82
|
| Published |
2004-3-15
|
| DOI |
10.4049/jimmunol.172.6.3876
|
| PMID |
15004195
|
| MeSH |
Adjuvants, Immunologic / biosynthesis
Adjuvants, Immunologic / metabolism
Adjuvants, Immunologic / physiology
Amino Acid Sequence
Animals
Antigens, Surface / biosynthesis
Antigens, Surface / metabolism
Antigens, Surface / physiology
Apoptosis* / immunology
Calcium-Binding Proteins
Carrier Proteins / biosynthesis*
Carrier Proteins / metabolism
Carrier Proteins / physiology
Cell Adhesion Molecules
Cell Line, Tumor
Cells, Cultured
Cricetinae
Cricetulus
Intercellular Signaling Peptides and Proteins
Leukemia P388
Macrophages / metabolism*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Milk Proteins / biosynthesis
Milk Proteins / metabolism
Molecular Sequence Data
NIH 3T3 Cells
Phagocytosis* / immunology
Phosphatidylserines / metabolism
Protein Binding / immunology
|
| IF |
4.886
|
| Resource |
| DNA material |
pEF-Del1/Flag (RDB18996)
pEF-Del1/D98E/Flag (RDB18997) |
