Inhibition of Natural Killer Cell Activity against Cytomegalovirus-Infected Fibroblasts by Nitric Oxide-Releasing Agents

The addition of nitric oxide (NO)-releasing agents, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC18), 3-{(±)-(E)-ethyl-2′-[(E)-hydroxyimino]-5-nitro-3-hexenecarbamoyl}-pyridine (NOR 4), significantly inhibited natural killer (NK) cell activity against cytomegalovirus (CMV)-infected cells. Inhibition of NK cell activity was due to NO released in the culture medium because the concentration of nitrite in the culture medium correlated with the inhibition of NK cell activity and the addition of an antagonist of NO, [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide] (carboxy-PTIO), to NK assay restored NK cell activity. The mechanism of inhibition of NK cell activity against CMV-infected cells by NO-releasing agents includes (1) inhibition of the production of interferon (IFN)-α by CD16 (Leu11b)-depleted cells cultured with CMV-infected cells and (2) inhibition of the activation process of NK cell by IFN-α. It is suggested that the production of NO by an inflammatory process may lead to the inhibition of NK cell-mediated cytotoxicity against CMV-infected cells.