Surface expression of phosphatidylserine on macrophages is required for phagocytosis of apoptotic thymocytes
Surface expression of phosphatidylserine on macrophages is required for phagocytosis of apoptotic thymocytes
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DOI：
10.1038/sj.cdd.4400690
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发表时间：
2000-07-01
影响因子：
12.4
通讯作者：
Schlegel, RA
中科院分区：
文献类型：
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作者：
Callahan, MK;Williamson, P;Schlegel, RA
细胞通常保持磷脂在质膜双层上的不对称分布，将磷脂、磷脂酰丝氨酸（PS）限制在质膜的内小叶。当细胞发生凋亡时，这种不对称的跨双层分布消失，将PS带到表面，在那里它作为吞噬细胞吞噬的信号。荧光染料mercury 540特异性地染色已经失去磷脂的不对称分布的凋亡细胞的质膜，然而，它也染色非凋亡的巨噬细胞，表明磷脂不对称性可能在这些细胞中不被维持，因此它们可能在其表面上表达PS。在这里，PS结合蛋白，膜联蛋白V，被用来表明，事实上正常的巨噬细胞表达PS在其表面上，此外，预处理巨噬细胞与膜联蛋白V被发现抑制吞噬凋亡的胸腺细胞和胸腺细胞上的PS表达被人工诱导，但不抑制吞噬乳胶珠或Fc受体介导的吞噬调理红细胞。这些结果表明，PS是组成型表达的巨噬细胞的表面上，是功能上的重要的PS表达的靶细胞的吞噬作用。
Cells generally maintain an asymmetric distribution of phospholipids across the plasma membrane bilayer, restricting the phospholipid, phosphatidylserine (PS), to the inner leaflet of the plasma membrane. When cells undergo apoptosis, this asymmetric transbilayer distribution is lost, bringing PS to the surface where it acts as a signal for engulfment by phagocytes. The fluorescent dye merocyanine 540 specifically stains the plasma membrane of apoptotic cells which have lost their asymmetric distribution of phospholipids, However, it also stains non-apoptotic macrophages, suggesting that phospholipid asymmetry may not be maintained in these cells, and thus that they may express PS on their surface. Here, the PS-binding protein, annexin V, was used to show that in fact normal macrophages do express PS on their surface, Furthermore, pre-treating macrophages with annexin V was found to inhibit phagocytosis of apoptotic thymocytes and thymocytes on which PS expression was artificially induced, but did not inhibit phagocytosis of latex beads or Fc receptor-mediated phagocytosis of opsonized erythrocytes. These results indicate that PS is constitutively expressed on the surface of macrophages and is functionally significant for the phagocytosis of PS-expressing target cells.