Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
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DOI：
10.4049/jimmunol.148.7.2207
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发表时间：
1992-04
影响因子：
4.4
通讯作者：
V. Fadok;D. Voelker;P. Campbell;J. Cohen;D. Bratton;P. Henson
中科院分区：
文献类型：
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作者：
V. Fadok;D. Voelker;P. Campbell;J. Cohen;D. Bratton;P. Henson
在正常组织重塑过程中，巨噬细胞会清除不需要的细胞，包括那些经历了程序性细胞死亡或凋亡的细胞。这种广泛的过程延伸到胸腺细胞的缺失（阴性选择），其中表达不适当Ag受体的细胞经历凋亡，并被胸腺巨噬细胞吞噬。尽管自梅奇尼科夫时代以来，巨噬细胞对无效白细胞的吞噬作用就已为人所知，但直到最近才认识到细胞凋亡会导致表面变化，从而允许在裂解之前识别和清除这些细胞。我们的数据表明，巨噬细胞特异性识别在细胞凋亡发展过程中暴露在淋巴细胞表面的磷脂酰丝氨酸。含有磷脂酰-L-丝氨酸的脂质体以剂量依赖性方式抑制凋亡淋巴细胞的巨噬细胞吞噬作用，但不被含有其他阴离子磷脂(包括磷脂酰-D-丝氨酸)的脂质体抑制。凋亡淋巴细胞的吞噬作用也受到与磷脂酰丝氨酸结构相关的化合物的 L 亚型的抑制，包括甘油磷酸丝氨酸和磷酸丝氨酸。与正常细胞相比，凋亡淋巴细胞的膜结合的部花青 540 染料的量增加，表明它们的膜脂堆积更加松散，这与膜磷脂不对称性的丧失一致。凋亡淋巴细胞在外部表达磷脂酰丝氨酸 (PS)，因为其表面的 PS 易于被荧光胺衍生化，并且因为凋亡细胞表达促凝血活性。这些观察结果表明，凋亡的淋巴细胞失去膜磷脂不对称性，并在质膜的外层暴露磷脂酰丝氨酸。巨噬细胞特异性识别暴露的 PS 后吞噬凋亡淋巴细胞。
During normal tissue remodeling, macrophages remove unwanted cells, including those that have undergone programmed cell death, or apoptosis. This widespread process extends to the deletion of thymocytes (negative selection), in which cells expressing inappropriate Ag receptors undergo apoptosis, and are phagocytosed by thymic macrophages. Although phagocytosis of effete leukocytes by macrophages has been known since the time of Metchnikoff, only recently has it been recognized that apoptosis leads to surface changes that allow recognition and removal of these cells before they are lysed. Our data suggest that macrophages specifically recognize phosphatidylserine that is exposed on the surface of lymphocytes during the development of apoptosis. Macrophage phagocytosis of apoptotic lymphocytes was inhibited, in a dose-dependent manner, by liposomes containing phosphatidyl-L-serine, but not by liposomes containing other anionic phospholipids, including phosphatidyl-D-serine. Phagocytosis of apoptotic lymphocytes was also inhibited by the L isoforms of compounds structurally related to phosphatidylserine, including glycerophosphorylserine and phosphoserine. The membranes of apoptotic lymphocytes bound increased amounts of merocyanine 540 dye relative to those of normal cells, indicating that their membrane lipids were more loosely packed, consistent with a loss of membrane phospholipid asymmetry. Apoptotic lymphocytes were shown to express phosphatidylserine (PS) externally, because PS on their surfaces was accessible to derivatization by fluorescamine, and because apoptotic cells expressed procoagulant activity. These observations suggest that apoptotic lymphocytes lose membrane phospholipid asymmetry and expose phosphatidylserine on the outer leaflet of the plasma membrane. Macrophages then phagocytose apoptotic lymphocytes after specific recognition of the exposed PS.