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

细胞粘附分子在动脉硬化发生过程中的作用及表达机制

基本信息

批准号：
07457562
负责人：
OKADA Masahiko
金额：
$ 4.86万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457562/
关键词：
preventive medicine arteriosclerosis vascular endothelial cell macrophage cellular adhesion molecule cell signaling oxidized LDL cytokine ダイトカイン

项目摘要

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.

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。通过用IL-1和TNF α激活观察到ELAM-1; IL-1在孵育1小时后急剧上升，并在2小时显示最大表达，而TNF α在30分钟后显示缓慢上升，并在4小时显示最大表达。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。