There is contention over whether human neutrophils produce physiologically significant levels of
nitric oxide (NO) during inflammatory reactions. Nevertheless, regardless of its cell source, NO does exert regulatory effects on neutrophil function. Depending on experimental conditions, NO can either inhibit or enhance neutrophil activation, in both cases probably acting through
cyclic GMP. The explanation for these apparently contradictory findings may be that the effect depends upon the concentration of NO: low concentrations of NO being stimulatory and high concentrations inhibitory.
Nitrite, produced at high concentrations from NO during
inflammation, can react with neutrophil
myeloperoxidase-derived
hypochlorous acid (HOCl) to form the active
oxidant nitryl chloride, a species capable of nitrating
tyrosine and tyrosyl residues on
proteins. Whether
nitryl chloride acts to limit or amplify the
oxidant effects of
myeloperoxidase is not yet clear, although formation of
nitrotyrosine has been linked with nitration of phagocytosed bacteria. Clearly, a better understanding of the inflammatory effects of NO on neutrophils is needed before the therapeutic potential of NO donors or inhibitors in
inflammation can be realised.