Seitz C S, Kleindienst R, Xu Q, Wick G
Institute for General and Experimental Pathology, Medical School, University of Innsbruck, Austria.
Lab Invest. 1996 Jan;74(1):241-52.
Bacterial cell-wall lipopolysaccharide (LPS) is the main endotoxin contributing to local inflammation and systemic toxicity during Gram-negative infections and induces aortic endothelial injury with or without cell death and replication followed by increased leukocyte adhesion. Heat-shock protein (hsp) 60 is under study in our laboratory as a potential antigen inducing immunologic attack to endothelial cells in atherogenesis. To investigate the mechanism of LPS-induced endothelial injury and the phenotypes of adhering cells, Lewis rats were treated in vivo or, in aortic organ cultures, with LPS to determine the expression of intercellular-adhesion molecule-1 (ICAM-1) and hsp60 on aortic endothelium and to characterize phenotypes of adhering leukocytes. Increased ICAM-1 expression by aortic endothelium was observed as early as 3 hr after LPS injection and persisted up to 72 hr, whereas elevated levels of hsp60 were found between 6 and 48 hr. In vitro application of various types of stress, such as LPS, H2O2, and high temperature, not only stimulated endothelial expression of hsp60 but, concomitantly, that of ICAM-1. The number of adhering leukocytes was significantly increased on aortic endothelium 6 hr after LPS administration, and the predominant leukocytes adhering to stressed endothelium were monocytes (80%) and T lymphocytes (8 to 20%). In organ cultures of rat aortic intimal, LPS, and H2O2 evoked increased leukocyte adhesion, which proved to be selective, because adherent leukocytes were mostly Ia+ monocytes and T cells, i.e., activated. Adhering T cells were gamma/delta antigen-receptor positive in 8 to 16% after LPS stress, whereas these cells amount to only 2 to 4% of peripheral blood T cells. Blocking of adhesion molecules ICAM-1, LFA-1 alpha, and/or LFA-1 beta reduced adhesion up to 34%. Increased coordinated LPS-dependent expression of hsp60 and ICAM-1 correlates with monocyte and T-cell adhesion to aortic endothelium. These observations may be significant for elucidating the mechanism of the initiating events in the development of atherosclerosis.
细菌细胞壁脂多糖（LPS）是革兰氏阴性菌感染期间导致局部炎症和全身毒性的主要内毒素，可诱导主动脉内皮损伤，无论有无细胞死亡和复制，随后白细胞黏附增加。热休克蛋白（hsp）60是我们实验室正在研究的一种潜在抗原，可在动脉粥样硬化形成过程中诱导对内皮细胞的免疫攻击。为了研究LPS诱导内皮损伤的机制以及黏附细胞的表型，对Lewis大鼠进行体内治疗，或在主动脉器官培养中用LPS处理，以确定细胞间黏附分子-1（ICAM-1）和hsp60在主动脉内皮上的表达，并对黏附白细胞的表型进行表征。LPS注射后3小时，主动脉内皮ICAM-1表达即开始增加，并持续至72小时，而hsp60水平在6至48小时升高。体外应用各种类型的应激，如LPS、H2O2和高温，不仅刺激内皮细胞hsp60的表达，同时也刺激ICAM-1的表达。LPS给药6小时后，主动脉内皮上黏附的白细胞数量显著增加，黏附于应激内皮的主要白细胞是单核细胞（80%）和T淋巴细胞（8%至20%）。在大鼠主动脉内膜的器官培养中，LPS和H2O2可引起白细胞黏附增加，这被证明具有选择性，因为黏附的白细胞大多是Ia+单核细胞和T细胞，即活化细胞。LPS应激后，8%至16%的黏附T细胞γ/δ抗原受体呈阳性，而这些细胞在外周血T细胞中仅占2%至4%。阻断黏附分子ICAM-1、LFA-1α和/或LFA-1β可使黏附减少达34%。hsp60和ICAM-1依赖LPS的协同表达增加与单核细胞和T细胞黏附于主动脉内皮相关。这些观察结果可能对阐明动脉粥样硬化发生发展起始事件的机制具有重要意义。
