EVIDENCE FOR THE ROLE OF SUPEROXIDE RADICALS IN NEUTROPHIL-MEDIATED CYTOTOXICITY

  • 1 January 1979
    • journal article
    • research article
    • Vol. 37  (2) , 301-309
Abstract
Human peripheral neutrophils became cytotoxic to chicken red blood cells (CRBC) in the presence of lectins as assessed by release of 51Cr from labeled target cells. Phytohemagglutinin (PHA) and concanavalin (Con)A, which caused time-dependent and dose-dependent cytotoxicity over a concentration range of 25-400 .mu.g/ml, caused significant generation of superoxide radicals 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 .mu.g/ml whereas catalytically inactive enzyme had no effect. Incubation under O2-depleted conditions caused a marked decrease in PHA-induced superoxide generation and cytotoxicity relative to that obtained with neutrophils incubated aerobically. A central role for superoxide radicals in causing target cell damage in this model of neutrophil-mediated cytotoxicity was suggested.