Goebeler M, Meinardus-Hager G, Roth J, Goerdt S, Sorg C
Institute of Experimental Dermatology, University of Münster, Germany.
J Invest Dermatol. 1993 Jun;100(6):759-65. doi: 10.1111/1523-1747.ep12476328.
Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) are endothelial surface molecules that play a role for leukocyte recruitment to sites of inflammation, e.g., during contact hypersensitivity. We studied the effects of sensitizing agents (2,4-dinitro-benzenesulfonic acid, metal salt haptens) and chemically related substances on endothelial adhesion molecule expression. Using flow cytometry and an enzyme-linked immunosorbent assay, NiCl2 and, to a lesser extent, CoCl2 were found to up-regulate ICAM-1, VCAM-1, and ELAM-1 expression on cultured human umbilical vein endothelium whereas the other substances tested showed no effects. Induction of adhesion molecules by NiCl2 required de novo mRNA and protein synthesis. Up-regulation could be blocked by kinase inhibitor H-7 but not staurosporine, suggesting involvement of phosphorylation events independent of protein kinase C activation. Concomitant application of NiCl2 and neutralizing antibodies to IL-1 did not block up-regulation by the hapten demonstrating that the latter did not act via an IL-1-dependent autocrine mechanism. Regarding ELAM-1 induction, pre-treatment for 24 h with NiCl2 produced hyporesponsiveness to IL-1 and TNF-alpha upon restimulation, suggesting that NiCl2 and these cytokines may partially share a common pathway of activation. In addition, analysis of cultured foreskin specimens revealed that NiCl2 may induce up-regulation of ELAM-1 on microvascular endothelium in vivo. Our data demonstrate that both Ni++ and Co++ to which simultaneous contact sensitivity is frequently observed have the ability to directly up-regulate endothelial adhesion molecules. This shared property may represent an adjuvant mechanism that promotes sensitization and elicitation events in contact hypersensitivity to these haptens.
细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和内皮细胞白细胞黏附分子-1（ELAM-1，E-选择素）是内皮表面分子，在白细胞募集到炎症部位（如接触性超敏反应期间）发挥作用。我们研究了致敏剂（2,4-二硝基苯磺酸、金属盐半抗原）和化学相关物质对内皮黏附分子表达的影响。使用流式细胞术和酶联免疫吸附测定法，发现氯化镍以及程度较轻的氯化钴可上调培养的人脐静脉内皮细胞上ICAM-1、VCAM-1和ELAM-1的表达，而测试的其他物质则无此作用。氯化镍诱导黏附分子需要从头合成mRNA和蛋白质。上调可被激酶抑制剂H-7阻断，但不能被星形孢菌素阻断，这表明磷酸化事件参与其中，且独立于蛋白激酶C激活。同时应用氯化镍和抗白细胞介素-1中和抗体并不能阻断半抗原引起的上调，这表明后者并非通过白细胞介素-1依赖性自分泌机制起作用。关于ELAM-1的诱导，用氯化镍预处理24小时后，再刺激时对白细胞介素-1和肿瘤坏死因子-α产生低反应性，这表明氯化镍与这些细胞因子可能部分共享一条共同的激活途径。此外，对培养的包皮标本的分析显示，氯化镍可能在体内诱导微血管内皮细胞上ELAM-1的上调。我们的数据表明，经常观察到同时存在接触性超敏反应的镍离子和钴离子都有直接上调内皮黏附分子的能力。这种共同特性可能代表一种佐剂机制，促进对这些半抗原的接触性超敏反应中的致敏和激发事件。
