Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells
Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells
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DOI：
10.1073/pnas.95.16.9535
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Masaki, T
中科院分区：
文献类型：
--
作者：
Oka, K;Sawamura, T;Masaki, T
磷脂酰丝氨酸(PS)暴露在质膜外表面的识别与衰老/凋亡细胞的吞噬作用有关。由于氧化低密度脂蛋白(OxLDL)被报道可阻断细胞吞噬功能，因此我们研究了内皮细胞中OxLDL受体1(LOX-1)是否介导内皮细胞对衰老/凋亡细胞的吞噬作用。培养的牛主动脉内皮细胞(BAE)和中国仓鼠卵巢(CHO)细胞表达牛LOX-1(BLOX-1-CHO)，但不表达野生型CHO-K1细胞、结合老化的红细胞(RBC)和凋亡细胞，并进一步吞噬细胞。在BAE和BLOX-1-CHO中，氧化低密度脂蛋白、乙酰化低密度脂蛋白等LOX-1配体均可抑制老化红细胞的结合和对凋亡细胞的吞噬作用，抗LOX-1的mAb可阻断老化红细胞与BAE的结合，提示LOX-1具有识别衰老细胞的作用。重组可溶性LOX-1抑制衰老/凋亡细胞与BLOX-1-CHO和BAE的相互作用，并将衰老红细胞与天然红细胞和凋亡细胞与天然细胞区分开来。PS脂质体抑制LOX-L介导的这些与衰老/凋亡细胞的相互作用，提示LOX-1识别凋亡细胞的PS。PS暴露在凋亡细胞表面是已知的促凝剂，因此，OxLDL的增加可能是动脉粥样硬化时凝血功能增强的原因之一，抑制了凋亡细胞的清除。
Recognition of the exposure of phosphatidylserine (PS) on the outer surface of plasma membrane has been implicated in the phagocytosis of aged/apoptotic cells. Because oxidized low-density lipoprotein (OxLDL) has been reported to block the phagocytosis, here we examined whether lectin-like OxLDL receptor 1 (LOX-1), the OxLDL receptor in endothelial cells, mediates phagocytosis of aged/apoptotic cells by endothelial cells. Cultured bovine aortic endothelial cells (BAE) and Chinese hamster ovary (CHO) cells expressing bovine LOX-1 (BLOX-1-CHO), but not wild-type CHO-K1 cells, bound aged red blood cells (RBC) and apoptotic cells, which were further phagocytosed. The binding of aged RBC and the phagocytosis of apoptotic cells were inhibited by OxLDL, acetyl LDL, and other LOX-1 ligands in both BAE and BLOX-1-CHO, mAb against LOX-1 blocked the binding of aged RBC to BAE, suggesting a role for LOX-1 in the recognition of aged cells, The recombinant soluble LOX-1 inhibited the interactions of aged/apoptotic cells with both BLOX-1-CHO and BAE and distinguished aged RBC from native RBC and apoptotic cells from native cells. PS liposome inhibited these LOX-l-mediated interactions with aged/apoptotic cells, suggesting LOX-1 recognizes PS of the apoptotic cells. PS exposed on the surface of apoptotic cells is known to be procoagulant, Accordingly, increased OxLDL may be one of the reasons for enhanced coagulation in atherosclerosis, inhibiting the removal of apoptotic cells.