Swerlick R A, Lee K H, Li L J, Sepp N T, Caughman S W, Lawley T J
Department of Dermatology, Emory University, Atlanta, GA 30322.
J Immunol. 1992 Jul 15;149(2):698-705.
Vascular endothelial cell adhesion molecule 1 (VCAM-1) is an adherence molecule that is induced on endothelial cells by cytokine stimulation and can mediate binding of lymphocytes or tumor cells to endothelium. Because these interactions often occur at the level of the microvasculature, we have examined the regulation of expression of VCAM-1 in human dermal microvascular endothelial cells (HDMEC) and compared it to the regulation of VCAM-1 in large vessel human umbilical vein endothelial cells (HUVEC). Both cell populations were judged pure as assessed by expression of von Willebrand factor and uptake of acetylated low density lipoprotein. Expression of VCAM-1 was not detectable on either unstimulated HDMEC or HUVEC when assessed by ELISA or flow cytometry. Stimulation of either HDMEC or HUVEC with TNF-alpha resulted in a time- and dose-dependent induction of VCAM-1. However, although TNF-alpha-induced cell surface and mRNA expression of VCAM-1 in HDMEC was transient, peaking after 16 h of stimulation, TNF stimulation led to persistently elevated cell surface expression of VCAM-1 on HUVEC. IL-1 alpha also induced cell surface expression of VCAM-1 on HUVEC in a time- and dose-dependent manner, but stimulation of HDMEC with IL-1 alpha at doses up to 1000 U/ml failed to induce significant cell surface expression. However, IL-1 alpha induced time- and dose-dependent increases in ICAM-1 on HDMEC. Similarly, IL-4 induced VCAM-1 expression and augmented TNF-alpha-induced expression on HUVEC but did not affect VCAM-1 expression on HDMEC. Binding of Ramos cells to cytokine-stimulated endothelial cell monolayers correlated with VCAM-1 induction. Increased binding was seen after stimulation of HDMEC with TNF-alpha, which was blocked by anti-VCAM-1 mAb, but no increases in binding were noted after stimulation of HDMEC monolayers with IL-1 alpha. These data provide additional evidence for the existence of endothelial cell heterogeneity and differences in cell adhesion molecule regulation on endothelial cells derived from different vascular beds.
血管内皮细胞黏附分子1（VCAM-1）是一种黏附分子，在细胞因子刺激下可在内皮细胞上诱导产生，能介导淋巴细胞或肿瘤细胞与内皮细胞的结合。由于这些相互作用通常发生在微血管水平，我们研究了人真皮微血管内皮细胞（HDMEC）中VCAM-1表达的调控，并将其与大血管人脐静脉内皮细胞（HUVEC）中VCAM-1的调控进行了比较。通过血管性血友病因子的表达和乙酰化低密度脂蛋白的摄取评估，判断这两种细胞群体均为纯合子。通过ELISA或流式细胞术评估时，未刺激的HDMEC或HUVEC上均未检测到VCAM-1的表达。用肿瘤坏死因子-α（TNF-α）刺激HDMEC或HUVEC会导致VCAM-1呈时间和剂量依赖性诱导。然而，尽管TNF-α诱导的HDMEC中VCAM-1的细胞表面和mRNA表达是短暂的，在刺激16小时后达到峰值，但TNF刺激导致HUVEC上VCAM-1的细胞表面表达持续升高。白细胞介素-1α（IL-1α）也以时间和剂量依赖性方式诱导HUVEC上VCAM-1的细胞表面表达，但用高达1000 U/ml的IL-1α刺激HDMEC未能诱导出明显的细胞表面表达。然而，IL-1α诱导HDMEC上细胞间黏附分子-1（ICAM-1）呈时间和剂量依赖性增加。同样，IL-４诱导HUVEC上VCAM-1表达并增强TNF-α诱导的表达，但不影响HDMEC上VCAM-1的表达。 Ramos细胞与细胞因子刺激的内皮细胞单层的结合与VCAM-1的诱导相关。用TNF-α刺激HDMEC后可见结合增加，这被抗VCAM-1单克隆抗体阻断，但用IL-1α刺激HDMEC单层后未观察到结合增加。这些数据为内皮细胞异质性的存在以及源自不同血管床的内皮细胞上细胞黏附分子调控的差异提供了额外证据。
