Tethering of Apoptotic Cells to Phagocytes through Binding of CD47 to Src Homology 2 Domain-Bearing Protein Tyrosine Phosphatase Substrate-1 1
Tethering of Apoptotic Cells to Phagocytes through Binding of CD47 to Src Homology 2 Domain-Bearing Protein Tyrosine Phosphatase Substrate-1 1
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DOI：
10.4049/jimmunol.171.11.5718
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发表时间：
2003-12
期刊：
影响因子：
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通讯作者：
K. Tada;Masato Tanaka;R. Hanayama;K. Miwa;A. Shinohara;A. Iwamatsu;S. Nagata
中科院分区：
文献类型：
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作者：
K. Tada;Masato Tanaka;R. Hanayama;K. Miwa;A. Shinohara;A. Iwamatsu;S. Nagata
凋亡细胞迅速被巨噬细胞和未成熟树突细胞吞噬。在这项研究中，我们发现一个小鼠巨噬细胞系（BAM 3）吞噬凋亡的胸腺细胞，但不是淋巴瘤细胞系（WR 19 L）。鉴定了抑制BAM 3对凋亡胸腺细胞的吞噬作用的mAb。纯化后的抗原为含Src同源2结构域的蛋白酪氨酸磷酸酶底物-1（SHPS-1）。SHPS-1的配体CD 47在小鼠胸腺细胞中表达，但在WR 19 L中不表达。当WR 19 L用CD 47转化时，转化子在诱导凋亡后可以被BAM 3吞噬。表达CD 47的WR 19 L转化体在体内比亲本WR 19 L更有效地被脾树突状细胞吞噬。掩蔽暴露在凋亡胸腺细胞上的磷脂酰丝氨酸抑制吞噬，而抗SHPS-1 mAb不仅抑制吞噬，而且抑制凋亡细胞与吞噬细胞的结合。这些结果表明，巨噬细胞需要凋亡细胞上的CD 47和磷脂酰丝氨酸进行吞噬，并表明CD 47和SHPS-1之间的相互作用在吞噬作用中起栓系步骤的作用。
Apoptotic cells are swiftly phagocytosed by macrophages and immature dendritic cells. In this study, we found that one mouse macrophage cell line (BAM3) engulfed apoptotic thymocytes, but not a lymphoma cell line (WR19L). mAbs that inhibited the phagocytosis of apoptotic thymocytes by BAM3 were identified. Purification of the Ag revealed that it was Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1 (SHPS-1). CD47, the ligand for SHPS-1, was expressed in mouse thymocytes, but not in WR19L. When WR19L was transformed with CD47, the transformants, after induction of apoptosis, could be phagocytosed by BAM3. The WR19L transformants expressing CD47 were more efficiently engulfed in vivo by splenic dendritic cells than the parental WR19L. Masking of the phosphatidylserine exposed on apoptotic thymocytes inhibited the engulfment, whereas the anti-SHPS-1 mAb inhibited not only the engulfment, but also the binding of apoptotic cells to phagocytes. These results indicate that macrophages require CD47 and phosphatidylserine on apoptotic cells for engulfment, and suggest that the interaction between CD47 and SHPS-1 works as a tethering step in the phagocytosis.