Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells
Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells
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DOI：
10.4049/jimmunol.172.6.3876
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发表时间：
2004-03-15
影响因子：
4.4
通讯作者：
Nagata, S
中科院分区：
文献类型：
--
作者：
Hanayama, R;Tanaka, M;Nagata, S
巨噬细胞的主要功能是吞噬。使细胞凋亡，以防止它们在死亡时释放有害物质。乳脂球-EGF-8(MFG-E8)是一种由激活的巨噬细胞分泌的糖蛋白，通过特异性识别暴露在凋亡细胞上的磷脂酰丝氨酸，在凋亡细胞和吞噬细胞之间起到桥梁作用。在本研究中，我们发现发育内皮细胞基因座-1(DEL-1)在结构和功能上与MFG-E8同源，它最初被鉴定为与α(V)β(3)整合素结合的胚胎内皮细胞蛋白。也就是说，两者都由一个信号序列、两个表皮生长因子结构域和两个因子VIII-同源结构域(C1和C2)组成。DEL-1通过因子VIII-同源结构域识别磷脂酰丝氨酸与细胞凋亡结合，亲和力与MFG-E8相似。Del-1通过Del-1中的表皮生长因子结构域与NIH3T3细胞表达的α(V)β(3)整合素相互作用，增强NIH3T3细胞对凋亡细胞的吞噬活性。对原代巨噬细胞和巨噬细胞系MFG-E8和Del-1表达的筛选表明，MFG-E8和Del-1在不同的巨噬细胞中均有表达。这些结果提示巨噬细胞亚群的存在，它们以不同的方式使用MFG-E8或Del-1吞噬凋亡细胞。
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 alpha(v)beta(3) 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 alpha(v)beta(3) 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.