Enhanced in vitro macrophage cytotoxicity against interferon-treated B16 melanoma cells.
Enhanced in vitro macrophage cytotoxicity against interferon-treated B16 melanoma cells.
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DOI：
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发表时间：
1995-10
影响因子：
3.2
通讯作者：
C. M. Fleischmann;W. R. Fleischmann
中科院分区：
文献类型：
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作者：
C. M. Fleischmann;W. R. Fleischmann
在体外维持在IFN-α中的小鼠B16黑色素瘤细胞（B16 α res细胞）中，对IFN-α体外抗增殖作用的抗性迅速发展。然而，当将B16 α res细胞注射到小鼠体内时，它们对IFN-α的抗肿瘤作用显著更敏感。这种增强的敏感性似乎至少部分是由于活化的巨噬细胞。为了研究B16 α res细胞的增强的巨噬细胞敏感性，已经使用B16和B16 α res细胞靶标进行了巨噬细胞介导的细胞毒性测定。在体外用IFN-γ激活的巯基乙酸盐诱导的腹腔巨噬细胞对B16和B16 α res细胞表现出剂量依赖性细胞毒性，但B16 α res靶细胞的细胞毒性水平显著更高。动力学实验结果表明，对B16 α res细胞的细胞溶解作用发生的速率比对B16细胞的细胞溶解作用快得多（孵育2 h的细胞毒性为50%，孵育24 h的细胞毒性为40%）。最后，来自B16接种小鼠的腹腔巨噬细胞对B16 α res细胞的细胞毒性也显著高于对B16细胞的细胞毒性。来自B16 α res接种小鼠的巨噬细胞对B16 α res细胞的细胞毒性显著高于来自B16接种小鼠的巨噬细胞。总之，这些观察结果提供了体外证据，支持腹膜巨噬细胞是增强宿主介导的抗B16 α res细胞抗肿瘤作用的重要介质的建议。
Resistance to the in vitro antiproliferative effects of INF-alpha rapidly develops in mouse B16 melanoma cells that are maintained in vitro in IFN-alpha (B16 alpha res cells). B16 alpha res cells, however, are significantly more sensitive to the antitumor effects of IFN-alpha when they are injected into mice. This enhanced sensitivity appears to be due, at least in part, to activated macrophages. To investigate enhanced macrophage sensitivity of B16 alpha res cells, macrophage-mediated cytotoxicity assays have been performed using both B16 and B16 alpha res cell targets. Thioglycollate-elicited peritoneal macrophages activated in vitro with IFN-gamma exhibited dose-dependent cytotoxicity against both B16 and B16 alpha res cells, but significantly higher levels of cytotoxicity occurred with B16 alpha res targets. Kinetics experiment results showed that the cytolytic effects against B16 alpha res cells occurred at a very much faster rate than the cytolytic effects against B16 cells (50% cytotoxicity with 2 h of incubation versus 40% cytotoxicity by 24 h, respectively). Finally, peritoneal macrophages from B16-inoculated mice also were significantly more cytotoxic against B16 alpha res cells than against B16 cells. Macrophages from B16 alpha res-inoculated mice were significantly more cytotoxic against B16 alpha res cells than were macrophages from B16-inoculated mice. Taken together, these observations provide in vitro evidence to support the suggestion that peritoneal macrophages are important mediators of the enhanced host-mediated antitumor effects against B16 alpha res cells.