Fricker S P, Slade E, Powell N A
AnorMed Inc., Langley, BC, Canada.
Anticancer Res. 1999 Jan-Feb;19(1A):553-6.
Nitric oxide, a proposed mediator of macrophage tumour cell killing, can react with superoxide to form peroxynitrite, which is capable of reacting with a variety of biological molecules. The RAW 264 murine macrophage cell line can be stimulated by cytokines and lipopolysaccharide to produce NO by induction of the inducible nitric oxide synthase. We have shown that activated RAW 264 cells are cytotoxic towards P815 murine mastocytoma cells, and that addition of a nitric oxide synthase inhibitor exerts a concentration dependent protective effect. Addition of superoxide dismutase had no effect on either RAW 264 NO production or cell killing. It was shown that RAW 264 cells do not undergo an oxidative burst. These results indicate that RAW 264 tumour cell killing is primarily a nitric oxide mediated event and does not involve macrophage-derived superoxide.
一氧化氮是一种被认为可介导巨噬细胞杀伤肿瘤细胞的介质，它能与超氧化物反应生成过氧亚硝酸根，而过氧亚硝酸根能够与多种生物分子发生反应。RAW 264小鼠巨噬细胞系可被细胞因子和脂多糖刺激，通过诱导诱导型一氧化氮合酶产生一氧化氮。我们已经表明，活化的RAW 264细胞对P815小鼠肥大细胞瘤细胞具有细胞毒性，并且添加一氧化氮合酶抑制剂会产生浓度依赖性的保护作用。添加超氧化物歧化酶对RAW 264细胞产生一氧化氮或细胞杀伤均无影响。结果表明，RAW 264细胞不会发生氧化爆发。这些结果表明，RAW 264细胞杀伤肿瘤细胞主要是一氧化氮介导的事件，并不涉及巨噬细胞衍生的超氧化物。
