THE ROLE OF REACTIVE OXYGEN METABOLITES IN THE TRANSCRIPTIONAL REGULATION OF IFN-GAMMA GENE-EXPRESSION BY HISTAMINE IN NK CELLS FOLLOWING IL-2 STIMULATION

The secretion of interferon-gamma (IFN-gamma) by natural killer (NK) c ells following in vitro stimulation with interleukin-2 (IL-2) is inhib ited by co-incubation with autologous monocytes al a transcriptional l evel by more than sixty-fold. In this study, we investigate the nature of the inhibitory signal and particularly the role of reactive oxygen metabolites (ROMs). It was found that the inhibition of IFN-gamma was operating at a pre-translational level, this was indicated by the ina bility of CD 56(+)-enriched natural killer cells to accumulate IFN-gam ma mRNA in the presence of elutriated monocytes. Both catalase, a scav enger of hydrogen peroxide and histamine, a biogenic amine which inhib its the generation of ROMs by monocytes, strongly abrogated the inhibi tion of IFN-gamma production. We thereby conclude that histamine behav es synergistically with IL-2 at a transcriptional level to induce IFN- gamma even in an admixture of NK cells and monocytes. (C) 1996 Academi c Press Limited