Nitric oxide and antimicrobial activity of reactive oxygen intermediates

It is well documented that nitric oxide contributes to the bactericidal activities of phagocytes. Murine activated neutrophils and macrophages produce both reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). However, only neutrophils in the presence of myeloperoxidase, produce an antimicrobial agent, hypochlorous acid (HOCl). Complex interactions of RNI (nitric oxide) with other antimicrobial agents of phagocytes are likely to exist, but these have not been clearly demonstrated. In this study, we treated bacteria (Escherichia coli) with the NO donor, S-nitrosoglutathione (GSNO) and hydrogen peroxide (H2O2) or HOCl. We found that exposure to H2O2 of the bacteria tested resulted in minimal toxicity. However the killing activities of H2O2 were potentiated by GSNO. On the contrary, the NO-donor completely abolished the bactericidal activity of HOCl. Our results indicate that NO-donating drugs in non toxic concentrations used for experimental purposes may strongly affect the cytotoxic activity of neutrophils and macrophages. We suggest that the similar interactions may exist at sites of inflammation.