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Letters to Nature

Nature 307, 276-278 (19 January 1984) | doi:10.1038/307276a0; Accepted 25 October 1983

Hydroxyl radical scavengers inhibit human natural killer cell activity

Manikkam Suthanthiran, Scott D. Solomon, Perry S. Williams, Albert L. Rubin, Abraham Novogrodsky & Kurt H. Stenzel

  1. Departments of Biochemistry and Medicine, The Rogosin Kidney Center, Cornell University Medical College, 1300 York Avenue, New York, New York 10021, USA
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As natural killer (NK) cell activity is an essential constituent of host defence systems1 and reactive oxygen intermediates participate in such defence2–4, the effect of scavengers of oxygen radicals on NK cell activity was investigated. Hydroxyl radical (OHdot) scavengers5 (dimethyl sulphoxide (DMSO), thiourea, dimethylurea, tetramethylurea, benzoic acid, ethanol, methanol and ethylene glycol) inhibited NK cell activity. Catalase, a scavenger of H2O2, and Superoxide dismutase (SOD), a scavenger of O-2, either alone or in combination, did not inhibit NK cell activity. Inhibition of the lipoxygenase pathway of arachidonic acid metabolism, a potential source of cellular OHdot, with nordihydroguaiaretic acid6 and 5,8,11,14-eicosatetraynoic acid (ETYA)7 resulted in marked inhibition of NK cell activity. Inhibition of the cyclooxygenase pathway7,8 with acetylsalicylic acid or indomethacin had minimal effects on NK cell activity. Taken together, these findings suggest that OHdot, possibly generated via the lipoxygenase pathway of arachidonic acid metabolism, is critical for NK cell cytotoxicity.