Ortaldo J R, Herberman R B, Harvey C, Osheroff P, Pan Y C, Kelder B, Pestka S
Proc Natl Acad Sci U S A. 1984 Aug;81(15):4926-9. doi: 10.1073/pnas.81.15.4926.
Most species of recombinant leukocyte interferons (IFN-alpha A, -alpha B, -alpha C, -alpha D, -alpha F, -alpha I, and -alpha K) were capable of boosting human natural killer (NK) activity after a 2-hr treatment of cells at a concentration of 1-80 units/ml. In contrast, recombinant human IFN-alpha J was found to be incapable of augmenting NK activity after exposure of cells for 2 hr to concentrations as high as 10,000 units/ml. This inability of IFN-alpha J to boost NK activity was not complete because, after exposure of cells to a high concentration of IFN-alpha J (10,000 units/ml) for 18 hr, boosting of cytolysis was observed. IFN-alpha J appeared to interact with receptors for IFN on NK cells since it was found to interfere with the boosting of NK activity by other species of IFN-alpha. In contrast to its deficient ability to augment NK activity, IFN-alpha J has potent antiviral and antiproliferative activities. Such extensive dissociation of these biological activities has not been observed previously with any other natural or recombinant IFN species. Thus, this IFN species may be useful for evaluating the relative importance of various biological activities on the therapeutic effects of IFN, for understanding structure-function relationships, and for determining the biochemical pathways related to the various biological effects of IFN.
大多数重组白细胞干扰素(IFN-αA、-αB、-αC、-αD、-αF、-αI和-αK)在以1-80单位/毫升的浓度对细胞进行2小时处理后,能够增强人类自然杀伤(NK)活性。相比之下,发现重组人IFN-αJ在细胞暴露于高达10000单位/毫升的浓度2小时后,无法增强NK活性。IFN-αJ无法增强NK活性并非完全如此,因为在细胞暴露于高浓度的IFN-αJ(10000单位/毫升)18小时后,观察到细胞溶解增强。IFN-αJ似乎与NK细胞上的IFN受体相互作用,因为发现它会干扰其他种类的IFN-α对NK活性的增强作用。与其增强NK活性的能力不足相反,IFN-αJ具有强大的抗病毒和抗增殖活性。以前在任何其他天然或重组IFN种类中都未观察到这些生物活性如此广泛的分离。因此,这种IFN种类可能有助于评估各种生物活性对IFN治疗效果的相对重要性,理解结构-功能关系,以及确定与IFN各种生物效应相关的生化途径。