SHORT COMMUNICATION: Oxygen Intermediates Are Required for Interferon Activation of NK Cells

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Abstract
Peripheral blood lymphocytes fractionated on Percoll density gradients were enriched five- to ten-fold in cytotoxicity again K562 target cells and in the frequency of cells bearing the HNK-1 marker and large-granular-lymphocyte (LGL) morphology of human NK cells. Few if any (3 CPM) which peaked 15 min after addition to these NK-enriched lymphocytes. Both the generation of chemiluminescence and augmentation of NK cytolysis against K562 by IFN were inhibited markedly (90%-100%) by catalase and the hydroxyl scavengers, benzoate, mannitol, and dimethylsulfoxide. Superoxide dismutase (SOD) had less of an effect (35%-70% inhibition) and heat-denatured SOD and catalase were not inhibitory. Inhibitors were only effective in blocking the interferon augmented portion of cytotoxicity if they were present during the IFN pretreatment period but not before or after. The scavengers were not directly toxic to the cells such that pretreated and washed lymphocytes retained normal function with respect to NK lysis and interferon activation in the absence of further inhibitors. The results suggest then that IFN may stimulate the production of low amounts of H2O2 and possibly other oxygen intermediates (OH•) which are a necessary event early in the pathway of IFN activation of human NK cells.