Xi T, Shi X, Guo D, Dong X, Xu X, Zhu D
Department of Biochemistry, Nanjing University, People's Republic of China.
Biochem Mol Biol Int. 1996 May;38(6):1183-9.
Biological activities of human tumor necrosis factor-alpha (hTNF-alpha) and its mutants were compared. In cytotoxicity assay with L929 cells, one mutant, designated as TNF-B, showed 4.5-fold higher activity than TNF examined. In receptor binding assay, TNF-B had almost the same affinity for TNF receptors on L929 cells as hTNF-alpha. We also found that TNF-B retained the cytotoxicity of hTNF-alpha for HEp-2 cells. TNF-B also had two-fold higher affinity than hTNF-alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested that TNF-B might still interact with the human TNF-R55 receptor, but it might largely lose its ability to bind to human TNF-R75. Changes of biological activity of TNFs might be due to an altered affinity to the different types of TNF receptor on the target cells.
对人肿瘤坏死因子-α（hTNF-α）及其突变体的生物学活性进行了比较。在对L929细胞的细胞毒性试验中，一种名为TNF-B的突变体表现出比所检测的TNF高4.5倍的活性。在受体结合试验中，TNF-B对L929细胞上的TNF受体的亲和力与hTNF-α几乎相同。我们还发现TNF-B保留了hTNF-α对HEp-2细胞的细胞毒性。TNF-B对HEp-2细胞（仅携带hTNF-R55）上的受体的亲和力也比hTNF-α高两倍，而对U937细胞（主要表达hTNF-R75）上的受体的亲和力较低。这些结果表明，TNF-B可能仍与人类TNF-R55受体相互作用，但它可能在很大程度上丧失了与人类TNF-R75结合的能力。TNFs生物学活性的变化可能是由于对靶细胞上不同类型TNF受体的亲和力改变所致。
