Hibbs J B, Taintor R R, Vavrin Z
Biochem Biophys Res Commun. 1984 Sep 17;123(2):716-23. doi: 10.1016/0006-291x(84)90288-2.
The experiments reported here provide a possible molecular mechanism for the activated macrophage cytotoxic effect. Tumor cells that develop cytostasis and inhibition of mitochondrial respiration in response to cocultivation with activated macrophages release a significant fraction of their intracellular iron-59 content. Kinetic studies show that specific release of iron-59 from target cells begins 4-6 hours after initiating cocultivation which is the time point that inhibition of DNA synthesis is first detected. Treatment of tumor cells with metabolic inhibitors causing inhibition of respiration, protein synthesis, RNA synthesis, and DNA synthesis to a similar or greater extent than that caused by activated macrophages does not induce release of intracellular iron-59. It is significant that mitochondrial respiration and DNA replication, both strongly inhibited in target cells by activated macrophages, are metabolic pathways with enzymatic activity vulnerable to inhibition by depletion of intracellular iron.
本文报道的实验为活化巨噬细胞的细胞毒性作用提供了一种可能的分子机制。与活化巨噬细胞共培养后出现细胞生长停滞和线粒体呼吸抑制的肿瘤细胞，会释放出其细胞内相当一部分的铁 - 59含量。动力学研究表明，从共培养开始4 - 6小时后，靶细胞开始特异性释放铁 - 59，而这个时间点也是首次检测到DNA合成受到抑制的时间。用代谢抑制剂处理肿瘤细胞，使其呼吸、蛋白质合成、RNA合成和DNA合成受到的抑制程度与活化巨噬细胞造成的抑制程度相似或更大，但这并不会诱导细胞内铁 - 59的释放。值得注意的是，活化巨噬细胞在靶细胞中强烈抑制的线粒体呼吸和DNA复制，都是酶活性易受细胞内铁耗竭抑制的代谢途径。
