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
DNA material pEF-Del1/Flag (RDB18996) pEF-Del1/D98E/Flag (RDB18997)