Lotzová E, Savary C A
J Interferon Res. 1984 Spring;4(2):201-13. doi: 10.1089/jir.1984.4.201.
We have studied the effect of two species of recombinant alpha interferon (IFN) on peripheral blood NK cell cytotoxicity of normal donors against K-562 target cell line. Both recombinant IFNs, species A (IFN-alpha rA) and species D (IFN-alpha rD) significantly augmented, in a dose-dependent manner, NK cell cytotoxic potential. Highest augmentation was achieved with doses in the range of 10(3)-10(4) u/ml. Augmentation was observed independently whether the IFN-alpha r was added directly to the cultures of the tumor and effector cells, or whether the effector cells were preincubated with IFN-alpha r. Increase in cytotoxicity was evident within 10 min of incubation with IFN-alpha rA and was further potentiated with increasing incubation time. In general, no synergistic effect of IFN-alpha rA and IFN-alpha rD was observed when both of these species were added together to target and effector cells. Studies on the mechanism of IFN-alpha r action demonstrated that neither species of IFN-alpha r affected NK cell tumor-binding potential, but augmented cytotoxic-tumor binding potential and maximum rate of lysis. NK cell recycling capacity of most of the donors was augmented by IFN-alpha rA. These data illustrate that pure preparations of IFN-alpha rA and IFN-alpha rD augmented NK cell antitumor potential in vitro, suggesting that these agents may have therapeutic potential in neoplasias when their mechanism of action is more understood, and optimal conditions for treatment are developed.
我们研究了两种重组α干扰素(IFN)对正常供体外周血NK细胞针对K-562靶细胞系的细胞毒性作用。两种重组IFN,即A种(IFN-αrA)和D种(IFN-αrD),均以剂量依赖的方式显著增强了NK细胞的细胞毒性潜能。在10³-10⁴u/ml的剂量范围内可实现最高增强效果。无论将IFN-αr直接添加到肿瘤细胞和效应细胞的培养物中,还是将效应细胞与IFN-αr预孵育,均观察到增强作用。与IFN-αrA孵育10分钟内细胞毒性即明显增加,并随着孵育时间延长而进一步增强。一般而言,当将这两种IFN-αr一起添加到靶细胞和效应细胞中时,未观察到协同作用。对IFN-αr作用机制的研究表明,两种IFN-αr均不影响NK细胞与肿瘤细胞的结合潜能,但增强了细胞毒性与肿瘤细胞的结合潜能以及最大裂解速率。IFN-αrA增强了大多数供体NK细胞的再循环能力。这些数据表明,IFN-αrA和IFN-αrD的纯制剂在体外增强了NK细胞的抗肿瘤潜能,这表明当对其作用机制有更深入了解并开发出最佳治疗条件时,这些药物在肿瘤治疗中可能具有治疗潜力。