Aarhus University Hospital, Research Laboratory for Biochemical Pathology, Aarhus C, Denmark; Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus C, Denmark; Department of Anesthesiology and Intensive Care, Randers Regional Hospital, Randers, Denmark.
Basic Clin Pharmacol Toxicol. 2013 Oct;113(4):273-9. doi: 10.1111/bcpt.12091. Epub 2013 Jul 6.
Endothelial activation is a pivotal event in the development and progression of inflammation. Central to endothelial activation is the up-regulation of cellular adhesion molecules (CAMs) including E-selectin (CD62E), ICAM-1 (CD54), VCAM-1 (CD106) and PECAM-1 (CD31). These CAMs are also found in soluble forms (sCAMs). In this in vitro study of endothelial activation, we examined whether the levels of sCAMs correlate with the endothelial surface expression of CAMs in a dose-dependent and time-dependent manner. Such a correlation would support the use of sCAMs as surrogate markers for endothelial activation in inflammatory conditions. Human umbilical vein endothelial cells (HUVEC) were cultured with various concentrations of TNF-α for 8 hr and at a fixed concentration of TNF-α for various durations. The levels of soluble and surface-bound E-selectin, ICAM-1, VCAM-1 and PECAM-1 were quantified by flow cytometry. TNF-α stimulation increased CAM and sCAM expression in a dose-dependent and time-dependent manner. There was a significant positive correlation between the levels of ICAM-1 and sICAM-1 and between the levels of VCAM and sVCAM-1 in both the dose-response and time-response experiments. A positive correlation between the levels of E-selectin and sE-selectin was observed in the time-response experiment. This study supports the use of sCAMs as potential biomarkers of endothelial activation. In particular, the use of sICAM-1, sVCAM-1 and sE-selectin seems promising.
内皮细胞活化是炎症发生和发展的关键事件。内皮细胞活化的核心是细胞黏附分子（CAMs）的上调，包括 E-选择素（CD62E）、细胞间黏附分子-1（CD54）、血管细胞黏附分子-1（CD106）和血小板内皮细胞黏附分子-1（CD31）。这些 CAMs 也以可溶性形式（sCAMs）存在。在这项内皮细胞活化的体外研究中，我们研究了 sCAMs 的水平是否与 CAMs 在剂量依赖性和时间依赖性方式下的内皮表面表达相关。这种相关性将支持使用 sCAMs 作为炎症条件下内皮细胞活化的替代标志物。用人脐静脉内皮细胞（HUVEC）与不同浓度的 TNF-α孵育 8 小时，并在固定浓度的 TNF-α下孵育不同时间。通过流式细胞术定量测定可溶性和表面结合的 E-选择素、ICAM-1、VCAM-1 和 PECAM-1 的水平。TNF-α刺激以剂量依赖性和时间依赖性方式增加 CAM 和 sCAM 的表达。在剂量反应和时间反应实验中，ICAM-1 和 sICAM-1 以及 VCAM 和 sVCAM-1 的水平之间均存在显著的正相关。在时间反应实验中，E-选择素和 sE-选择素的水平之间存在正相关。这项研究支持使用 sCAMs 作为内皮细胞活化的潜在生物标志物。特别是，sICAM-1、sVCAM-1 和 sE-选择素的使用似乎很有前景。
