Silberstein D S, David J R
Proc Natl Acad Sci U S A. 1986 Feb;83(4):1055-9. doi: 10.1073/pnas.83.4.1055.
Tumor necrosis factor (TNF) is a monocyte product that kills or inhibits the growth of certain tumor cells. Its cell source and physical characteristics suggest that it is similar to a monokine, eosinophil-cytotoxicity-enhancing factor (M-ECEF), that activates human eosinophil toxicity to Schistosoma mansoni larvae. The availability of recombinant human TNF allowed us to test this possibility. The data show that TNF has no direct effect on the parasites but enhances eosinophil toxicity to the parasites in a dose-dependent fashion. This effect is specific for eosinophils and not neutrophils. TNF and the eosinophil-specific activity of TNF are coeluted with M-ECEF in reversed-phase HPLC. Further, M-ECEF activity in HPLC fractions is reduced by treatment with rabbit anti-TNF antibody and protein A-Sepharose. This demonstrates physical similarity and at least partial immunological identity of TNF and a fraction of M-ECEF. Thus, TNF can enhance eosinophil function and may constitute an important immunological regulatory mechanism. This effect should be considered when TNF is applied clinically.
肿瘤坏死因子(TNF)是一种单核细胞产物,可杀死或抑制某些肿瘤细胞的生长。其细胞来源和物理特性表明,它类似于一种单核因子,即嗜酸性粒细胞细胞毒性增强因子(M-ECEF),该因子可激活人类嗜酸性粒细胞对曼氏血吸虫幼虫的毒性。重组人TNF的可得性使我们能够测试这种可能性。数据表明,TNF对寄生虫没有直接作用,但能以剂量依赖的方式增强嗜酸性粒细胞对寄生虫的毒性。这种作用对嗜酸性粒细胞具有特异性,对中性粒细胞则无此作用。在反相高效液相色谱法中,TNF和TNF的嗜酸性粒细胞特异性活性与M-ECEF共洗脱。此外,用兔抗TNF抗体和蛋白A-琼脂糖处理后,高效液相色谱馏分中的M-ECEF活性降低。这证明了TNF与一部分M-ECEF在物理上具有相似性,且至少在免疫方面具有部分同一性。因此,TNF可增强嗜酸性粒细胞功能,可能构成一种重要的免疫调节机制。在临床应用TNF时应考虑到这种作用。