Leeuwenberg J F, van Tits L J, Jeunhomme T M, Buurman W A
Department of Surgery, University of Limburg, Maastricht, The Netherlands.
Cytokine. 1995 Jul;7(5):457-62. doi: 10.1006/cyto.1995.0062.
The current study was undertaken to investigate the role of TNF-R75 in regulation of E-selectin and ICAM-1 expression by TNF on HUVEC. To this end, we used agonistic anti-TNF-R75 antibodies, being mAb MR2-1 and polyclonal antibodies anti-TNF-R75 (pAb75). The agonistic properties of these antibodies were ascertained by the costimulatory capacity in a T-cell proliferation assay. These anti-TNF-R75 antibodies bound effectively to HUVEC, as evidenced in binding studies using 125I-TNF, but they did not induce or enhance E-selectin or ICAM-1 expression as did agonistic anti-TNF-R55 antibodies. In contrast, both MR2-1 and pAb75 inhibited specifically TNF-induced E-selectin and ICAM-1 expression, but not activation by IL-1 or LPS. These results support the hypothesis, that in cells responding to TNF via the signalling pathway of the TNF-R55, the extracellular part of TNF-R75 captures TNF and delivers it to TNF-R55, resulting in an enhanced response to TNF.
本研究旨在探究TNF-R75在肿瘤坏死因子（TNF）对人脐静脉内皮细胞（HUVEC）的E-选择素和细胞间黏附分子-1（ICAM-1）表达调控中的作用。为此，我们使用了激动性抗TNF-R75抗体，即单克隆抗体MR2-1和多克隆抗TNF-R75抗体（pAb75）。这些抗体的激动特性通过T细胞增殖试验中的共刺激能力得以确定。这些抗TNF-R75抗体能有效结合HUVEC，这在使用125I-TNF的结合研究中得到证实，但它们不像激动性抗TNF-R55抗体那样诱导或增强E-选择素或ICAM-1的表达。相反，MR2-1和pAb75均特异性抑制TNF诱导的E-选择素和ICAM-1表达，但不抑制白细胞介素-1（IL-1）或脂多糖（LPS）的激活。这些结果支持了以下假设：在通过TNF-R55信号通路对TNF作出反应的细胞中，TNF-R75的细胞外部分捕获TNF并将其传递给TNF-R55，从而增强对TNF的反应。
