Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells.
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.
Department of Genetics, Osaka University Medical School, Osaka, Japan.
Rikinari
R
Hanayama
Masato
M
Tanaka
Keiko
K
Miwa
Shigekazu
S
Nagata
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis / Q000276:immunology; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D036341:Intercellular Signaling Peptides and Proteins; D007941:Leukemia P388; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010587:Phagocytosis / Q000276:immunology; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D010718:Phosphatidylserines