Oka K, Sawamura T, Kikuta K, Itokawa S, Kume N, Kita T, Masaki T
Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto 606 Japan.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9535-40. doi: 10.1073/pnas.95.16.9535.
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-1-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.
血浆膜外表面磷脂酰丝氨酸（PS）的暴露已被认为与衰老/凋亡细胞的吞噬作用有关。由于据报道氧化低密度脂蛋白（OxLDL）会阻断吞噬作用，因此我们在此研究内皮细胞中的OxLDL受体——凝集素样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）和表达牛LOX-1的中国仓鼠卵巢（CHO）细胞（BLOX-1-CHO），而非野生型CHO-K1细胞，能够结合衰老红细胞（RBC）和凋亡细胞，并进一步将其吞噬。在BAE和BLOX-1-CHO中，OxLDL、乙酰化LDL及其他LOX-1配体均可抑制衰老RBC的结合及凋亡细胞的吞噬作用。抗LOX-1单克隆抗体可阻断衰老RBC与BAE的结合，提示LOX-在识别衰老细胞中发挥作用。重组可溶性LOX-1可抑制衰老/凋亡细胞与BLOX-1-CHO和BAE的相互作用，并区分衰老RBC与天然RBC以及凋亡细胞与天然细胞。PS脂质体可抑制这些由LOX-1介导的与衰老/凋亡细胞的相互作用，表明LOX-1可识别凋亡细胞的PS。已知暴露于凋亡细胞表面的PS具有促凝作用。因此，OxLDL增加可能是动脉粥样硬化中凝血增强的原因之一，它抑制了凋亡细胞的清除。
