A receptor for phosphatidylserine-specific clearance of apoptotic cells
A receptor for phosphatidylserine-specific clearance of apoptotic cells
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DOI：
10.1038/35011084
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发表时间：
2000-05-04
期刊：
影响因子：
64.8
通讯作者：
Henson, PM
中科院分区：
文献类型：
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作者：
Fadok, VA;Bratton, DL;Henson, PM
体内细胞凋亡的高潮是吞噬细胞尸体。在细胞凋亡过程中，质膜磷脂的不对称性丧失，从而使磷脂酰丝氨酸暴露在外部（1-4）。凋亡细胞的吞噬作用可被磷脂酰丝氨酸及其结构类似物立体特异性抑制，但不被其他阴离子磷脂抑制，表明磷脂酰丝氨酸被特异性识别（1，5 -10）。利用噬菌体展示，我们克隆了一个基因，似乎识别磷脂酰丝氨酸凋亡细胞。在这里，我们表明，这个基因，当转染到B和T淋巴细胞，使他们能够识别和吞噬凋亡细胞的磷脂酰丝氨酸特异性的方式。使用单克隆抗体的流式细胞术分析表明，该蛋白质在巨噬细胞，成纤维细胞和上皮细胞的表面上表达;这种抗体，如磷脂酰丝氨酸脂质体，抑制凋亡细胞的吞噬作用，并在巨噬细胞中，诱导抗炎状态。这一候选磷脂酰丝氨酸受体是高度同源的秀丽隐杆线虫和果蝇中的未知功能的基因，这表明，磷脂酰丝氨酸识别凋亡细胞在其清除过程中的吞噬细胞是高度保守的整个胚胎发育。
The culmination of apoptosis in vivo is phagocytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally(1-4). The phagocytosis of apoptotic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogues, but not by other anionic phospholipids, suggesting that phosphatidylserine is specifically recognized(1,5-10). Using phage display, we have cloned a gene that appears to recognize phosphatidylserine on apoptotic cells. Here we show that this gene, when transfected into B and T lymphocytes, enables them to recognize and engulf apoptotic cells in a phosphatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macrophages, fibroblasts and epithelial cells; this antibody, like phosphatidylserine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrophages, induced an anti-inflammatory state. This candidate phosphatidylserine receptor is highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highly conserved throughout phylogeny.