Expression of Developmental Endothelial Locus-1 in a Subset of Macrophages for Engulfment of Apoptotic Cells

• Published in: The Journal of immunology (1950) 2004-03, Vol.172 (6), p.3876-3882
• Main Authors: Hanayama, Rikinari, Tanaka, Masato, Miwa, Keiko, Nagata, Shigekazu
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - biosynthesis; Adjuvants, Immunologic - metabolism; Adjuvants, Immunologic - physiology; Amino Acid Sequence; Animals; Antigens, Surface - biosynthesis; Antigens, Surface - metabolism; Antigens, Surface - physiology; Apoptosis - immunology; Carrier Proteins - biosynthesis; Carrier Proteins - metabolism; Carrier Proteins - physiology; Cell Line, Tumor; Cells, Cultured; Cricetinae; Cricetulus; Del-1 protein; Leukemia P388; Macrophages - metabolism; MFG-E8 glycoprotein; Mice; Mice, Inbred C57BL; Mice, Transgenic; milk fat globule; Milk Proteins - biosynthesis; Milk Proteins - metabolism; Molecular Sequence Data; NIH 3T3 Cells; Phagocytosis - immunology; Phosphatidylserines - metabolism; Protein Binding - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.6.3876

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.