OXIDIZED LOW-DENSITY-LIPOPROTEIN INDUCES THE EXPRESSION OF P-SELECTIN (GMP140/PADGEM/CD62) ON HUMAN ENDOTHELIAL-CELLS
OXIDIZED LOW-DENSITY-LIPOPROTEIN INDUCES THE EXPRESSION OF P-SELECTIN (GMP140/PADGEM/CD62) ON HUMAN ENDOTHELIAL-CELLS
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DOI：
10.1042/bj3060293
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发表时间：
1995-02-15
影响因子：
4.1
通讯作者：
MCGREGOR, JL
中科院分区：
文献类型：
--
作者：
GEBUHRER, V;MURPHY, JF;MCGREGOR, JL
现在已经确定，单核细胞粘附于由氧化低密度脂蛋白（LDL）激活的内皮细胞。然而，在氧化低密度脂蛋白损伤后，内皮细胞上参与结合单核细胞的粘附受体仍有待阐明。在这项研究中，我们研究了天然或氧化 LDL 对 P-选择素表达的影响。天然 LDL (N-LDL) 通过与内皮细胞 (EC-LDL) 或铜 (Cu-LDL) 一起孵育或在作为对照的培养基中 (C-LDL) 进行氧化。使用抗 P-选择素 (CD62) 单克隆抗体 (LYP20) 测定 P-选择素的表达。结果表明，EC-LDL 和 Cu-LDL，而非 N-LDL 或 C-LDL，可诱导人脐静脉内皮细胞 (HUVEC) 表达 P-选择素。低浓度（20μg/ml）LDL诱导的P-选择素与LDL颗粒的氧化状态直接相关。此外，高浓度（100μg/ml）的N-LDL也可通过诱导P-选择素表达来激活HUVEC。这种表达在 LDL 激活的内皮细胞上持续超过 1 小时，而凝血酶或组胺激活的内皮细胞的 P-选择素水平在诱导后 15-20 分钟内下降。与P-选择素相反，E-选择素不能被低浓度或高浓度氧化LDL处理的内皮细胞诱导。本研究结果表明，氧化 LDL 处理的内皮细胞表达的 P-选择素参与介导单核细胞系 (U937) 或外周血单核细胞中单核细胞的粘附。抗 P-选择素单克隆抗体 (LYP20) 抑制 U937 细胞和单核细胞的结合。这些结果强烈表明P-选择素参与动脉粥样硬化形成的早期阶段。
It is now well established that monocytes adhere to endothelial cells activated by oxidized low-density lipoproteins (LDL). However, the adhesive receptors on endothelial cells involved in binding monocytes, following an insult by oxidized LDL, remains to be elucidated. In this study we have looked at the effect of native or oxidized LDL on the expression of P-selectin. Native LDL (N-LDL) was oxidized by incubation with either endothelial cells (EC-LDL) or copper (Cu-LDL), or in culture medium as a control (C-LDL). Expression of P-selectin was assayed with an anti-P-selectin (CD62) monoclonal antibody (LYP20). Results show that EC-LDL and Cu-LDL, but not N-LDL or C-LDL, induce the expression of P-selectin by human umbilical-vein endothelial cells (HUVECs). Induction of P-selectin by low concentrations (20 mu g/ml) of LDL is directly related to the state of oxidation of the LDL particles. In addition, high concentrations (100 mu g/ml) of N-LDL also activate HUVECs by inducing P-selectin expression. This expression was sustained for a period of over 1 h on LDL-activated endothelial cells, in contrast with thrombin- or histamine-activated endothelial cells, whose P-selectin levels fall within 15-20 min after induction. E-selectin, in contrast with P-selectin, could not be induced by endothelial cells treated with low or high concentrations of oxidized LDL. Results in this study show that P-selectin expressed by oxidized-LDL-treated endothelial cells are involved in mediating the adhesion of a monocytic cell line (U937) or monocytes in peripheral-blood mononuclear cells. An anti-P-selectin monoclonal antibody (LYP20) inhibited the binding of U937 cells and monocytes. These results strongly suggest that P-selectin is involved in the early stages of atherogenesis.