EFFECT OF AROMATIC NITROSO-COMPOUNDS ON SUPEROXIDE-GENERATING ACTIVITY IN NEUTROPHILS

Aromatic nitroso-compounds such as nitrosobenzene inhibited the respir atory burst of intact neutrophils induced by various stimulants, inclu ding phorbol 12-myristate 13-acetate and a chemotactic peptide. The co mpounds also inhibited NADPH-dependent oxygen consumption by cell-free preparations of neutrophils. This indicates that nitroso-compounds ac t directly on the NADPH-oxidase system. The inhibitory effects induced by several nitroso-compounds, 2-nitrosotoluene, nitrosobenzene, 4-nit rosophenol, and 1-nitrosopyrrolidine, were examined and their inhibiti on constants, the concentrations causing 50% reduction of oxygen consu mption, were found to be 0.043, 0.173, 0.672, and 32.1 mM, respectivel y, These values correlated well with the hydrophobicity of the compoun ds: a more hydrophobic compound was a more potent inhibitor against NA DPH oxidase, suggesting that the oxidase has a hydrophobic site(s) for interaction with the inhibitors.