McCarron R M, Wang L, Siren A L, Spatz M, Hallenbeck J M
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Proc Soc Exp Biol Med. 1994 Mar;205(3):257-62. doi: 10.3181/00379727-205-43706.
The intercellular adhesion of circulating leukocytes to vascular endothelium is a prerequisite for leukocyte emigration from the blood to extravascular tissues. This process is facilitated by adhesion molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the first time that the leukocyte adhesion receptor, intercellular adhesion molecule-1, is constitutively expressed on cultured cerebromicrovascular endothelial cell lines derived from both spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. Both cultures contained similar numbers of cells constitutively expressing this adhesion molecule (31.4% and 29.6%, respectively). Adhesion molecule expression was up-regulated by interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma and lipopolysaccharide in a dose- and time-dependent manner. Both cultures exhibited similar maximum levels of adhesion molecule up-regulation to optimal concentrations of all three cytokines. However, SHR endothelial cells were more sensitive to all three cytokines; significantly higher levels of intercellular adhesion molecule-1 expression were seen on SHR as opposed to WKY endothelial cells cultured with sub-optimal cytokine concentrations. It was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothelial cells to a greater extent than on WKY endothelial cells. The findings that intercellular adhesion molecule-1 can be up-regulated to a greater degree on SHR endothelial cells may have important implications for in vivo perivascular leukocyte accumulation under hypertensive conditions. These observations indicate a possible mechanism by which hypertension may predispose to the development of disorders such as atherosclerosis and stroke.
循环白细胞与血管内皮细胞的细胞间黏附是白细胞从血液迁移至血管外组织的前提条件。血管内皮细胞和白细胞表面的黏附分子促进了这一过程。本文所展示的实验首次证明，白细胞黏附受体——细胞间黏附分子-1，在源自自发性高血压（SHR）大鼠和正常血压的Wistar-Kyoto（WKY）大鼠的培养脑微血管内皮细胞系中组成性表达。两种培养物中组成性表达这种黏附分子的细胞数量相似（分别为31.4%和29.6%）。白细胞介素-1β、肿瘤坏死因子-α、干扰素-γ和脂多糖以剂量和时间依赖性方式上调黏附分子的表达。两种培养物对所有三种细胞因子的最佳浓度均表现出相似的黏附分子上调最大水平。然而，SHR内皮细胞对所有三种细胞因子更为敏感；与用次优细胞因子浓度培养的WKY内皮细胞相比，在SHR内皮细胞上观察到细胞间黏附分子-1表达水平显著更高。还观察到脂多糖对SHR内皮细胞上细胞间黏附分子-1表达的上调程度大于对WKY内皮细胞的上调程度。细胞间黏附分子-1在SHR内皮细胞上可被更大程度上调这一发现，可能对高血压条件下体内血管周围白细胞积聚具有重要意义。这些观察结果表明了一种可能的机制，通过该机制高血压可能易患动脉粥样硬化和中风等疾病。
