Klostergaard J, Leroux M E
Department of Tumor Biology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Biochem Biophys Res Commun. 1989 Dec 29;165(3):1262-6. doi: 10.1016/0006-291x(89)92738-1.
We have investigated the role of L-arginine in macrophage tumor cytotoxicity in coculture. L929, EMT-6, MCA-26, and P815 targets were all susceptible to cytolysis by activated macrophages when cocultured in medium containing L-arginine. When cocultured in arginine-free medium, these targets displayed comparable or even higher levels of lysis. L1210 targets were lytically resistant under either condition. However, 59Fe release from this target did reflect strong dependence on the presence of arginine. The structural analogue, NG-monomethyl-L-arginine, was an effective inhibitor of iron-release from L1210 targets cocultured with activated macrophages, whereas it had minimal inhibitory effects on release of 51Cr from cocultured L929 cells. These results suggest that the L-arginine requiring cytotoxic pathway of activated macrophage is independent of major effector mechanisms involved in tumor cell lysis.
我们研究了L-精氨酸在共培养体系中巨噬细胞肿瘤细胞毒性中的作用。当L929、EMT-6、MCA-26和P815靶细胞在含L-精氨酸的培养基中共培养时，它们均易被活化的巨噬细胞溶解。当在无精氨酸的培养基中共培养时，这些靶细胞表现出相当甚至更高水平的溶解。L1210靶细胞在两种条件下均具有溶解抗性。然而，该靶细胞释放的59Fe确实反映出对精氨酸存在的强烈依赖性。结构类似物NG-单甲基-L-精氨酸是与活化巨噬细胞共培养的L1210靶细胞铁释放的有效抑制剂，而对共培养的L929细胞释放51Cr的抑制作用最小。这些结果表明，活化巨噬细胞所需的L-精氨酸细胞毒性途径独立于参与肿瘤细胞溶解的主要效应机制。
