Evidence for the role of superoxide radicals in neutrophil-mediated cytotoxicity.
Evidence for the role of superoxide radicals in neutrophil-mediated cytotoxicity.
复制标题
超氧自由基在中性粒细胞介导的细胞毒性中作用的证据。
作者：
L. Simchowitz;I. Spilberg
人外周血中性粒细胞在凝集素存在下对鸡红细胞（CRBC）具有细胞毒性，通过从标记的靶细胞释放51铬进行评估。植物血凝素（PHA）和伴刀豆球蛋白A（ConA）在25- 400 μ g/ml浓度范围内引起时间依赖性和剂量依赖性的细胞毒性，用铁细胞色素C还原法测定，它们也引起超氧自由基的显著产生。美洲商陆有丝分裂原在相同浓度范围内不诱导细胞毒性，不能促进中性粒细胞产生超氧化物。PHA诱导产生超氧化物歧化酶，并出现在PHA依赖的细胞毒性之前。超氧化物歧化酶（SOD）能酶促破坏超氧化物，在100- 500 μ g/ml浓度范围内对PHA依赖的细胞毒性有中度抑制作用，而无催化活性的酶则无此作用。缺氧条件下的孵育导致PHA诱导的超氧化物生成和细胞毒性相对于嗜中性粒细胞需氧孵育获得显着减少。这些研究结果表明，在这种嗜中性粒细胞介导的细胞毒性模型中，超氧自由基在引起靶细胞损伤中起着重要作用。
Human peripheral neutrophils became cytotoxic to chicken red blood cells (CRBC) in the presence of lectins as assessed by release of 51chromium from labelled target cells. Phytohaemagglutinin (PHA) and concanavalin A (Con A), which caused time-dependent and dose-dependent cytotoxicity over a concentration range of 25--400 microgram/ml, also caused significant generation of superoxide radicals as measured by ferricytochrome C reduction. Pokeweed mitogen, which does not induce cytotoxicity over the same concentration range, was unable to promote superoxide generation by neutrophils. PHA-induced generation of superoxide paralleled and appeared to precede PHA-dependent cytotoxicity. Superoxide dismutase (SOD), which enzymatically destroys superoxide, caused moderate inhibition of PHA-dependent cytotoxicity over the concentration range of 100--500 microgram/ml whereas catalytically inactive enzyme had no effect. Incubation under oxygen-depleted conditions caused a marked decrease in both PHA-induced superoxide generation and cytotoxicity relative to that obtained with neutrophils incubated aerobically. These findings suggest a central role for superoxide radicals in causing target cell damage in this model of neutrophil-mediated cytotoxicity.