Keller R, Bassetti S, Keist R, Mülsch A, Klauser S
Immunobiology Research Group, Institute for Immunology and Virology, University of Zurich, Switzerland.
Biochem Biophys Res Commun. 1992 May 15;184(3):1364-71. doi: 10.1016/s0006-291x(05)80033-6.
Various bacteria and bacterial products induce in pure, lymphocyte-free bone marrow-derived mononuclear phagocytes (BMMø) the generation of tumor necrosis factor, nitric oxide (NO) synthase, NO and nitrite (NO2-), the flow of L-arginine to citrulline, and tumoricidal activity. The flow of L-arginine to citrulline and formation of NO/NO2- on the one hand and expression of tumoricidal activity were not always closely related; however, these parameters were suppressed in a dose-dependent manner by the flavoprotein inhibitor, diphenyleneiodonium (DPI) and the L-arginine analogue, NG-monomethyl-L-arginine (NMMA). The findings support the concept of a central role of the NO synthase pathway in the generation of tumor necrosis factor-independent tumoricidal activity by activated macrophages but the exact conditions which enable the transfer of the lytic principle from the effector to the target cell remain to be elucidated.
多种细菌及细菌产物可在纯净的、不含淋巴细胞的骨髓来源单核吞噬细胞（BMMø）中诱导肿瘤坏死因子、一氧化氮（NO）合酶、NO和亚硝酸盐（NO2-）的产生，L-精氨酸向瓜氨酸的转化，以及杀肿瘤活性。一方面，L-精氨酸向瓜氨酸的转化及NO/NO2-的形成与杀肿瘤活性的表达并不总是密切相关；然而，黄素蛋白抑制剂二苯乙烯碘鎓（DPI）和L-精氨酸类似物NG-单甲基-L-精氨酸（NMMA）以剂量依赖方式抑制了这些参数。这些发现支持了NO合酶途径在活化巨噬细胞产生不依赖肿瘤坏死因子的杀肿瘤活性中起核心作用的概念，但使溶解原理从效应细胞传递至靶细胞的确切条件仍有待阐明。
