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.

动脉内皮细胞中粘附分子的表达是动脉硬化开始期间的关键事件。我们的研究表明，内皮细胞偶尔表达内皮白细胞粘附分子1（ELAM-1），但通过氧化的LDL，糖化的LDL，H_2O_2和低氧培养基培养基培养基。同样重要的因子是氧化的LDL及其自身抗体的免疫复合物。接下来，我们检查了人胸主动脉培养的内皮细胞中ELMA-1，ELMA-1，细胞间粘附分子1（ICAM-1）和血管细胞粘附Mplecule-1（VCAM-1）的时间关系。所检查的激活剂是IL-1Alpha（10ng/ml），TNFalpha（10ng/ml）和Infgamma（10ng/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在一个小时孵育后急剧上升，并在2小时时显示最大表达，而TNFALPHA在30分钟后显示出缓慢的上升，最大增加在4小时时。观察到ICAM-1表达在未刺激的细胞中EVN，并与激活持续时间成比例增加。 IL-1和TNFALPHA对ICAM-1表达的影响没有显着差异。孵育2小时后，仅通过TNFalphA才能观察到VCAM-1的轻微表达。 Infgamma不会引起ELAM-1，VCAM-1和ICAM-1的表达变化。目前的数据表明，每种诱导ELAM-1和VCAM-1的诱导似乎都有特定的信号途径，而不是ICAM-1。因此，在动脉粥样硬化中，分子的时间关系可能对内皮细胞区分单核细胞与其他细胞（如中性粒细胞）起作用。