Roles and Expression Mechanisms of Cellular Adhesion Molecules during the Initiation of Arteriosclerosis

黏附分子在动脉内皮细胞中的表达是动脉硬化发病过程中的重要事件。我们的研究表明，在体外，氧化型低密度脂蛋白、糖化低密度脂蛋白、H_2O_2和低氧培养液中，内皮细胞偶尔但显著地表达内皮细胞白细胞黏附分子-1(ELAM-1)。氧化低密度脂蛋白免疫复合物及其自身抗体也是重要因素。接下来，我们研究了在培养的人胸主动脉内皮细胞中诱导ELMA-1、细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的时间关系。激活剂为IL-1α(10 ng/m L)、肿瘤坏死因子α(10 ng/m l)和干扰素-γ(10 ng/m L)。每种细胞因子与细胞孵育0.5-48小时。IL-1和TNFα共同激活ELAM-1，IL-1在孵育1小时后急剧升高，2小时达最大表达，而TNFα在30分钟后缓慢升高，4小时达最大。ICAM-1在未受刺激的细胞中有表达，并随激活时间的延长而增加。IL-1和TNFα对ICAM-1表达的影响无显著差异。仅在孵育2小时后，肿瘤坏死因子α才观察到VCAM-1的微弱表达。INFGamma对ELAM-1、VCAM-1和ICAM-1的表达无明显影响。目前的数据表明，ELAM-1和VCAM-1的每次诱导似乎都有特定的信号通路，但没有ICAM-1。因此，在动脉粥样硬化形成过程中，分子间的时间关系可能起到内皮细胞区分单核细胞和中性粒细胞等其他细胞的作用。

Expressions of the adhesion molecules in arterial endothelial cells are crucial events during the initiation of arteriosclerosis. Our study showed that endothelial cells expressed endothelial leukocyte adhesion molecule-1 (ELAM-1) occasionally but significantly by oxidized LDL,glycated LDL,H_2O_2, and hypoxic culture mediumin vitro. Also significant factor was immune-complex of oxidized LDL and its auto-antibody. Next we examined temporal relations of induction of ELMA-1, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion mplecule-1 (VCAM-1) in cultured endothelial cells of human thoracic aorta. Activators examined were IL-1alpha (10ng/mL), TNFalpha (10ng/mL), and INFgamma (10ng/mL). Cells were incubated with each of the cytokines for 0.5-48 hours. ELAM-1 was observed by the activations with IL-1 and TNFalpha ; IL-1 gave a sharp rise after an hour incubation and showed the maximum expression at 2 hours, while TNFalpha showed a slow rise after 30 minutes and the maximum at 4 hours. ICAM-1 expression was observed evn in non-stimulated cells and further increased in proportion to duration of the activation. There was no significant difference between the effects of IL-1 and TNFalpha to the ICAM-1 expression. Slight expression of VCAM-1 was observed only by TNFalpha after 2-hours incubation. INFgamma did not cause any change in the expression of ELAM-1, VCAM-1, and ICAM-1. The present data indicate that there appear to be specific signal pathways for each induction of ELAM-1 and VCAM-1, but not ICAM-1. In atherogenesis, therefore, the temporal relations of the molecules may play a role for endothelial cells to discriminate monocytes from other cells such as neutrophils.