跨膜型和分泌型TNF-α对TNF受体作用的比较

A COMPARISON BETWEEN THE EFFECTS OF TRANS MEMBRANE AND SECRETORY TUMOR NECROSIS FACTORα ON TUMOR NECROSIS FACTOR RECEPTORS

用可溶性ＴＮＦＲ预先与ｍＴＮＦα或ｓＴＮＦα温育可明显抑制两型ＴＮＦ随后的胞毒效应；用ｓＴＮＦ封闭靶细胞的ＴＮＦＲ可抑制随后ｓＴＮＦ对之的胞毒效应，却不能影响ｍＴＮＦ的作用。提示ｍＴＮＦ与ｓＴＮＦ一样是依赖ＴＮＦＲ发挥作用的，但二者与ＴＮＦＲ结合位点不同。比较两型ＴＮＦ对表达不同类型ＴＮＦＲ靶细胞的胞毒效应，对ｓＴＮＦ敏感的靶细胞主要表达ＴＮＦＲＩ，而ｍＴＮＦ则对表达Ⅰ型和／或Ⅱ型ＴＮＦＲ的靶细胞均有杀伤作用。抗ＴＮＦＲ抗体与ｍＴＮＦ相似，可杀伤对ｓＴＮＦ耐受肿瘤细胞系；将其预先与靶细胞作用并不能封闭ｍＴＮＦ的杀瘤效应，提示二者与ＴＮＦＲ结合位点不同。

おt is still a matter in dispute whether the bioactivity of membraneassociated form of tumor necrosis factorα(mTNFα) is TNF receptor (TNFR)dependent. In the present study, it has been shown that preincubation of both forms of TNF with soluble TNFR markedly inhibited their cytotoxic effect on target cells. Blocking of target cell TNFRs by sTNF depressed the cytotoxicity of sTNF on these cells, but has no influence on the effect of mTNF on the same target cells. These results suggest that the effect of both mTNF and sTNF is TNFR dependent, while the binding sites of these two forms of TNF may be different. In comparing the cytotoxic effects of the two forms of TNF on cell lines expressing different TNFR types, we noticed that cells primarily expressing TNFRⅠ were sensitive to sTNF, while those expressing TNFRⅠ and/or TNFRⅡ could be killed by mTNF. As was mTNF, antibodies against TNFR were also cytotoxic to tumor cell lines resistant to sTNF. The cytotoxicity of mTNF was not influenced by preincubation its target cells with antiTNFR McAbs suggesting a difference in TNFRbinding sites and a possible similarity in the transcellular signal transduction between these two substances.