Pace J L
Department of Comparative and Experimental Pathology, University of Florida, Gainesville.
J Leukoc Biol. 1988 Dec;44(6):514-20. doi: 10.1002/jlb.44.6.514.
The ability of MuIFN-beta and MuIFN-gamma to potentiate the development of tumoricidal activity in proteose peptone-elicited murine peritoneal macrophages was investigated. Macrophages were stimulated with increasing concentrations of either MuIFN-beta or MuIFN-gamma, alone and in combination, in the presence of 1 ng/ml lipopolysaccharide (LPS). The priming activities attributable to the interferons (IFNs) were quantified using the dose-response curves obtained for these samples. The priming activity observed for mixtures of MuIFN-beta and MuIFN-gamma was greater than that expected if MuIFN-beta and MuIFN-gamma had acted in an additive manner. Isobologram analysis of data obtained when macrophages were stimulated with combinations of IFNs demonstrated that MuIFN-beta and MuIFN-gamma acted synergistically to prime macrophages for tumor cell killing. The greatest degree of synergy was observed when macrophages were stimulated with suboptimal and nearly equivalent concentrations of each class of IFN. Further studies demonstrated that macrophages stimulated with combinations of MuIFN-beta and MuIFN-gamma were more sensitive to the trigger signal provided by LPS than were cells primed with either IFN alone. Thus, the synergistic effects observed were quantitative in nature in that macrophages perceived combinations of MuIFN-beta and MuIFN-gamma as having higher priming activities than expected.
研究了鼠干扰素-β（MuIFN-β）和鼠干扰素-γ（MuIFN-γ）增强蛋白胨诱导的小鼠腹腔巨噬细胞杀瘤活性的能力。在存在1 ng/ml脂多糖（LPS）的情况下，用递增浓度的MuIFN-β或MuIFN-γ单独及联合刺激巨噬细胞。使用这些样品获得的剂量反应曲线对干扰素（IFN）的启动活性进行定量。观察到的MuIFN-β和MuIFN-γ混合物的启动活性大于MuIFN-β和MuIFN-γ以相加方式作用时预期的活性。当用IFN组合刺激巨噬细胞时，对所得数据进行等效线图分析表明，MuIFN-β和MuIFN-γ协同作用启动巨噬细胞杀伤肿瘤细胞。当用次优且几乎等效浓度的每种IFN刺激巨噬细胞时，观察到最大程度的协同作用。进一步的研究表明，与单独用任一IFN启动的细胞相比，用MuIFN-β和MuIFN-γ组合刺激的巨噬细胞对LPS提供的触发信号更敏感。因此，观察到的协同效应本质上是定量的，因为巨噬细胞认为MuIFN-β和MuIFN-γ的组合具有比预期更高的启动活性。
