BINDING AND PHAGOCYTOSIS OF APOPTOTIC VASCULAR SMOOTH-MUSCLE CELLS IS MEDIATED IN PART BY EXPOSURE OF PHOSPHATIDYLSERINE
BINDING AND PHAGOCYTOSIS OF APOPTOTIC VASCULAR SMOOTH-MUSCLE CELLS IS MEDIATED IN PART BY EXPOSURE OF PHOSPHATIDYLSERINE
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DOI：
10.1161/01.res.77.6.1136
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发表时间：
1995-12-01
影响因子：
20.1
通讯作者：
TAIT, JF
中科院分区：
文献类型：
--
作者：
BENNETT, MR;GIBSON, DF;TAIT, JF
近年来研究表明，血管平滑肌细胞在体内外均可发生凋亡。凋亡细胞被摄取到邻近的正常细胞中似乎是快速和特异的。我们研究了正常平滑肌细胞单层对凋亡血管平滑肌细胞的结合和吞噬作用。用原癌基因c-myc或腺病毒E1 A基因感染血管平滑肌细胞，诱导其在低血清条件下发生凋亡，然后与正常平滑肌细胞孵育。细胞凋亡伴随着细胞外表面上的磷脂酰丝氨酸暴露的显着增加，这是通过结合膜联蛋白V.脂质体含有磷脂酰丝氨酸，但不磷脂酰肌醇抑制凋亡细胞的摄取以剂量依赖性的方式，最大的50%的抑制;膜联蛋白V也抑制凋亡细胞的摄取以剂量依赖性和钙依赖性的方式。凋亡小体的结合似乎不是由内源性膜联蛋白V介导的，如膜联蛋白V的抗体不能抑制摄取所证明的。平滑肌细胞也能够识别其他细胞类型上暴露的磷脂酰丝氨酸，这是通过它们结合具有高度暴露的磷脂酰丝氨酸的红细胞的能力来判断的。我们的结论是，平滑肌细胞表达磷脂酰丝氨酸在凋亡过程中，这种曝光部分介导的结合和吞噬死细胞。这种机制可能在促进血管壁中的快速细胞去除方面很重要。
Apoptosis of vascular smooth muscle cells has recently been demonstrated to occur in vitro and in vivo. Uptake of apoptotic cells into adjacent normal cells appears to be rapid and specific. We have investigated binding and phagocytosis of apoptotic vascular smooth muscle cells by normal smooth muscle cell monolayers. Vascular smooth muscle cells were infected with the proto-oncogene c-myc or the adenovirus E1A gene, induced to undergo apoptosis in low-serum conditions, and then incubated with normal smooth muscle cells. Apoptosis was accompanied by a marked increase in exposure of phosphatidylserine on the outer surface of the cell, which was recognized by binding to annexin V. Liposomes containing phosphatidylserine but not phosphatidylinositol inhibited uptake of apoptotic cells in a dose-dependent manner to a maximum of 50% inhibition; annexin V also inhibited the uptake of apoptotic cells in a dose-dependent and calcium-dependent manner. Binding of apoptotic bodies did not appear to be mediated by endogenous annexin V, as evidenced by the inability of an antibody to annexin V to inhibit uptake. Smooth muscle cells were also able to recognize exposed phosphatidylserine on other cell types, as judged by their ability to bind erythrocytes having a high degree of exposed phosphatidylserine. We conclude that smooth muscle cells express phosphatidyl-serine during apoptosis, and this exposure partly mediates binding and phagocytosis of dead cells. This mechanism may be important in promoting rapid cell removal in the vessel wall.