title: Evidence for the role of superoxide radicals in neutrophil-mediated cytotoxicity.
abstract: 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.
mesh_terms: D002374:Catalase / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D010100:Oxygen / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000096:biosynthesis / Q000502:physiology*; D013997:Time Factors
chemical_list: D037102:Lectins; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase; D009113:Muramidase; D010100:Oxygen