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

血管内皮细胞粘附分子的表达是动脉硬化发生发展的重要环节。本研究发现，在体外培养条件下，氧化LDL、糖化LDL、H_2O_2和缺氧均可引起内皮细胞表达内皮细胞白细胞粘附分子-1（ELAM-1）。氧化型低密度脂蛋白及其自身抗体的免疫复合物也是重要因素。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、细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1）的时间关系。检查的激活剂为IL-1 α（10 ng/mL）、TNF α（10 ng/mL）和INF γ（10 ng/mL）。将细胞与每种细胞因子孵育0.5-48小时。通过IL-1和TNFalpha的激活观察到ELAM-1; IL-1在孵育1小时后急剧上升，在2小时达到最大表达，而TNFalpha在30分钟后缓慢上升，在4小时达到最大表达。ICAM-1的表达，观察evn在非刺激的细胞，并进一步增加的激活的持续时间成比例。IL-1和TNF α对ICAM-1表达的影响无显著性差异。孵育2小时后，仅通过TNF α观察到VCAM-1的轻微表达。INF γ未引起ELAM-1、VCAM-1和ICAM-1表达的任何变化。目前的数据表明，ELAM-1和VCAM-1的每种诱导似乎都有特定的信号通路，但ICAM-1没有。因此，在动脉粥样硬化形成中，这些分子的时间关系可能对内皮细胞区分单核细胞和其他细胞（如中性粒细胞）起作用。

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.