PT  - JOURNAL ARTICLE
AU  - Hanayama, Rikinari
AU  - Tanaka, Masato
AU  - Miwa, Keiko
AU  - Nagata, Shigekazu
TI  - Expression of Developmental Endothelial Locus-1 in a Subset of Macrophages for Engulfment of Apoptotic Cells
AID  - 10.4049/jimmunol.172.6.3876
DP  - 2004 Mar 15
TA  - The Journal of Immunology
PG  - 3876--3882
VI  - 172
IP  - 6
4099  - http://www.jimmunol.org/content/172/6/3876.short
4100  - http://www.jimmunol.org/content/172/6/3876.full
SO  - J. Immunol.2004 Mar 15; 172
AB  - 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 αvβ3 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 αvβ3 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.