Immunoregulatory and antimicrobial effects of nitrogen oxides.

The therapeutic effects of inhaled nitric oxide (NO) therapy are thought to be restricted to the pulmonary vasculature because of rapid inactivation of NO by hemoglobin in the bloodstream. However, recent data suggest that inhaled NO may not only be scavenged by the heme iron of hemoglobin but also may react with protein thiols in the bloodstream, including cysteine-93 of the hemoglobin B subunit. Reaction of NO with protein or peptide thiols is termed S-nitrosylation and results in the formation of relatively stable protein S-nitrosothiols that carry NO bioactivity to distal organs. Thus, inhaled NO-induced protein S-nitrosylation may allow inhaled NO to have multiple as yet undiscovered physiologic and pathophysiologic effects outside of the lung. Here we review the immunoregulatory and antimicrobial functions of NO and the potential effects of inhaled NO therapy on host defense.