Wellicome S M, Thornhill M H, Pitzalis C, Thomas D S, Lanchbury J S, Panayi G S, Haskard D O
Rheumatology Unit, United Medical and Dental School, London, UK.
J Immunol. 1990 Apr 1;144(7):2558-65.
The alteration in the surface of endothelial cells (EC) in response to cytokines is likely to be of great importance to the regulation of cell migration and thereby to the evolution of inflammatory processes. We have generated three mAb against cytokine inducible Ag on EC. Whereas mAb 1.2B6 and 6.5B5 were found to react with ELAM-1 and ICAM-1, respectively, mAb 1.4C3 reacted with a novel molecule that showed a different pattern of expression from ELAM-1 or ICAM-1 after stimulation of EC by TNF, IL-1, or LPS. Like ELAM-1, the 1.4C3 Ag was minimally expressed on resting EC, whereas ICAM-1 was moderately expressed. After stimulation with IL-1, TNF, or LPS, ELAM-1 expression was maximal after 4 to 6 h, 1.4C3 Ag after 6 to 10 h, and ICAM-1 after 10 to 24 h. The duration of 1.4C3 expression was intermediate between ELAM-1 and ICAM-1, and was more prolonged in response to TNF than IL-1 or LPS. Whereas the expression of the three Ag showed a similar dose response to varying concentrations of IL-1 or LPS, EC required a 10-fold higher concentration of TNF for half maximal expression of ELAM-1 than for half maximal expression of 1.4C3 Ag or ICAM-1 (5 ng/ml compared to 0.5 ng/ml). Of the three Ag, only ICAM-1 was enhanced by IFN-gamma. SDS-PAGE under reducing conditions showed the 1.4C3 Ag to migrate as a single band with a relative molecular mass of approximately 95 kDa. mAb 1.4C3 adds to our understanding of the kinetics of the EC response to different cytokines and will be useful in studying the regulation of EC activation. Furthermore, the 1.4C3 molecule may have an important role in leukocyte-EC interactions.
内皮细胞（EC）表面因细胞因子而发生的改变可能对细胞迁移的调节以及炎症过程的演变极为重要。我们制备了三种针对内皮细胞上细胞因子诱导抗原的单克隆抗体（mAb）。发现单克隆抗体1.2B6和6.5B5分别与ELAM-1和ICAM-1反应，而单克隆抗体1.4C3与一种新分子反应，该分子在肿瘤坏死因子（TNF）、白细胞介素-1（IL-1）或脂多糖（LPS）刺激内皮细胞后，其表达模式与ELAM-1或ICAM-1不同。与ELAM-1一样，1.4C3抗原在静息内皮细胞上表达极少，而ICAM-1呈中度表达。用IL-1、TNF或LPS刺激后，ELAM-1在4至6小时表达达到最大值，1.4C3抗原在6至10小时，ICAM-1在10至24小时。1.4C3表达的持续时间介于ELAM-1和ICAM-1之间，并且对TNF的反应比对IL-1或LPS的反应更持久。尽管这三种抗原的表达对不同浓度的IL-1或LPS表现出相似的剂量反应，但内皮细胞使ELAM-1达到最大表达量一半所需的TNF浓度比使1.4C3抗原或ICAM-1达到最大表达量一半所需的浓度高10倍（分别为5 ng/ml和0.5 ng/ml）。在这三种抗原中，只有ICAM-1能被γ干扰素增强。在还原条件下进行的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）显示，1.4C3抗原迁移为一条相对分子质量约为95 kDa的单带。单克隆抗体1.4C3增进了我们对内皮细胞对不同细胞因子反应动力学的理解，将有助于研究内皮细胞激活的调节。此外，1.4C3分子可能在白细胞与内皮细胞的相互作用中起重要作用。
