Beran M, Andersson B S, Kelleher P, Whalen K, McCredie K, Gutterman J
Blood. 1987 Mar;69(3):721-6.
In vitro characteristics of response to recombinant tumor necrosis factors alpha (rTNF-alpha) and beta (rTNF-beta) were studied in six human myelogenous leukemia cell lines. Heterogeneity of the response to rTNF was observed, and one line (K562) was resistant. No enhancement of cell growth was noted in any cell line. The dose-response curves for rTNF-alpha were characteristically sigmoid, the maximum inhibitory effect occurring between 25 and 200 ng/mL. Nonresponsiveness within this range indicated resistance that could not be overcome, even with very high doses of rTNF alpha. A similar response of sensitive and resistant lines occurred after exposure to rTNF-beta. The clonogenic cells were more sensitive than the overall population to the action of rTNF alpha, and prolonged exposure was necessary for manifestation of the effect. Concomitant exposure to recombinant interferon-alpha (rIFN-alpha) increased the response of two cell lines to rTNF-alpha, but no clear synergistic action could be demonstrated. The addition of rIFN-gamma was without effect. Variations in the rTNF-alpha-induced proliferative response could not be explained by differences in the number of binding sites per cell or their affinity for rTNF-alpha. That the clonogenic cells showed a higher sensitivity than the whole population might indicate a preferential effect on more primitive, actively proliferating cells with high growth potential.
在六种人骨髓性白血病细胞系中研究了对重组肿瘤坏死因子α（rTNF-α）和β（rTNF-β）的体外反应特性。观察到对rTNF的反应存在异质性，其中一个细胞系（K562）具有抗性。在任何细胞系中均未观察到细胞生长增强。rTNF-α的剂量反应曲线呈典型的S形，最大抑制作用出现在25至200 ng/mL之间。在此范围内无反应表明存在抗性，即使使用非常高剂量的rTNF-α也无法克服。暴露于rTNF-β后，敏感和抗性细胞系出现类似反应。克隆形成细胞比总体细胞群体对rTNF-α的作用更敏感，且需要长时间暴露才能显现出效果。同时暴露于重组干扰素α（rIFN-α）可增加两个细胞系对rTNF-α的反应，但未显示出明显的协同作用。添加rIFN-γ没有效果。rTNF-α诱导的增殖反应变化无法用每个细胞的结合位点数量或其对rTNF-α的亲和力差异来解释。克隆形成细胞比总体细胞群体表现出更高的敏感性，这可能表明对更原始、具有高生长潜力且活跃增殖的细胞具有优先作用。
