Engelmann H, Holtmann H, Brakebusch C, Avni Y S, Sarov I, Nophar Y, Hadas E, Leitner O, Wallach D
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
J Biol Chem. 1990 Aug 25;265(24):14497-504.
Immunological cross-reactivity between tumor necrosis factor (TNF) binding proteins which are present in human urine (designated TBPI and TBPII) and two molecular species of the cell surface receptors for TNF is demonstrated. The two TNF receptors are shown to be immunologically distinct, to differ in molecular weight (58,000 and 73,000), and to be expressed differentially in different cells. It is further shown that polyclonal antibodies against one of the TNF binding proteins (TBPI) display, by virtue of their ability to bind the TNF receptor, activities which are very similar to those of TNF. These antibodies are cytotoxic to cells which are sensitive to TNF toxicity, induce resistance to TNF toxicity, enhance the incorporation of thymidine into normal fibroblasts, inhibit the growth of chlamydiae, and induce the synthesis of prostaglandin E2. Monovalent F(ab) fragments of the polyclonal antibodies lack TNF-like activities, but acquire them upon cross-linking with anti-F(ab)2 antibodies, suggesting that the ability of the anti-TBPI antibodies to mimic TNF correlates with their ability to cross-link the TNF receptors. This notion was further supported by data obtained in a comparative study of the TNF-like cytotoxicity of a panel of monoclonal antibodies against TBPI. The induction of TNF-like effects by antibodies to a TNF receptor suggests that TNF is not directly involved in intracellular signalling. Rather, it is the receptors to this cytokine which, when properly triggered in a process which appears to involve clustering of these receptors, transduce the signal for response to TNF into the cell's interior.
已证实存在于人类尿液中的肿瘤坏死因子（TNF）结合蛋白（命名为TBPI和TBPII）与TNF细胞表面受体的两种分子形式之间存在免疫交叉反应性。这两种TNF受体在免疫学上是不同的，分子量不同（分别为58,000和73,000），并且在不同细胞中差异表达。进一步表明，针对其中一种TNF结合蛋白（TBPI）的多克隆抗体，由于其能够结合TNF受体，表现出与TNF非常相似的活性。这些抗体对TNF毒性敏感的细胞具有细胞毒性，可诱导对TNF毒性的抗性，增强胸苷掺入正常成纤维细胞，抑制衣原体生长，并诱导前列腺素E2的合成。多克隆抗体的单价F(ab)片段缺乏TNF样活性，但与抗F(ab)2抗体交联后会获得这些活性，这表明抗TBPI抗体模拟TNF的能力与其交联TNF受体的能力相关。一组针对TBPI的单克隆抗体的TNF样细胞毒性的比较研究数据进一步支持了这一观点。针对TNF受体的抗体诱导TNF样效应表明TNF不直接参与细胞内信号传导。相反，是这种细胞因子的受体，当在一个似乎涉及这些受体聚集的过程中被适当触发时，将对TNF的反应信号转导到细胞内部。
