Komatsu S, Panés J, Russell J M, Anderson D C, Muzykantov V R, Miyasaka M, Granger D N
Department of Physiology, LSU Medical Center, Shreveport 71130-3932, USA.
Hypertension. 1997 Feb;29(2):683-9. doi: 10.1161/01.hyp.29.2.683.
Recent reports indicate that bacterial endotoxin (lipopolysaccharide) and cytokines elicit a more profound increase in the surface expression of intercellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells derived from spontaneously hypertensive (SHR) versus normotensive Wistar-Kyoto rats (WKY). Our objective in this study was to characterize and compare in vivo ICAM-1 expression in SHR and WKY under basal conditions and after 5 hours of endothelial cell activation with either lipopolysaccharide (5 mg/kg i.p.) or tumor necrosis factor-alpha (TNF-alpha; 1, 5, and 10 micrograms/kg i.p.). ICAM-1 expression was quantified in different tissues by the double-radiolabeled monoclonal antibody technique. When constitutive (baseline) ICAM-1 expression was corrected for endothelial cell surface area, significantly higher values were noted in SHR than WKY but only in splanchnic organs. Lipopolysaccharide and TNF-alpha elicited significant increases in ICAM-1 expression in all tissues of both WKY and SHR. However, the magnitude of the lipopolysaccharide-induced ICAM-1 upregulation in heart, stomach, skeletal muscle, and brain was significantly lower in SHR than WKY. A similar blunted ICAM-1 upregulation was noted in the stomach of SHR after administration of 5 micrograms/kg TNF-alpha. The differences in induced ICAM-1 expression between SHR and WKY do not appear to be due to differences in endothelial cell surface area or plasma glucocorticoid levels. These results suggest that chronic arterial hypertension results in altered ICAM-1 expression on the endothelium, which may contribute to the abnormal inflammatory responses associated with this disease.
最近的报告表明，与正常血压的Wistar-Kyoto大鼠（WKY）相比，细菌内毒素（脂多糖）和细胞因子可使源自自发性高血压大鼠（SHR）的培养内皮细胞中细胞间黏附分子-1（ICAM-1）的表面表达显著增加。本研究的目的是在基础条件下以及用脂多糖（5mg/kg腹腔注射）或肿瘤坏死因子-α（TNF-α；1、5和10μg/kg腹腔注射）激活内皮细胞5小时后，对SHR和WKY体内ICAM-1的表达进行表征和比较。通过双放射性标记单克隆抗体技术对不同组织中的ICAM-1表达进行定量。当根据内皮细胞表面积校正组成性（基线）ICAM-1表达时，发现SHR中的值显著高于WKY，但仅在内脏器官中如此。脂多糖和TNF-α均可使WKY和SHR的所有组织中ICAM-1表达显著增加。然而，SHR心脏、胃、骨骼肌和脑中脂多糖诱导的ICAM-1上调幅度显著低于WKY。在给予5μg/kg TNF-α后，SHR的胃中也观察到类似的ICAM-1上调减弱。SHR和WKY之间诱导的ICAM-1表达差异似乎并非由于内皮细胞表面积或血浆糖皮质激素水平的差异。这些结果表明，慢性动脉高血压导致内皮细胞上ICAM-1表达改变，这可能导致与该疾病相关的异常炎症反应。
