Reactive nitrogen intermediates and antimicrobial activity: role of nitrite.
The reactive nitrogen intermediate (RNI) nitric oxide (NO.) is formed from L-arginine by an NO. synthase and, following secondary reactions yielding additional toxic intermediates, nitrite (NO2-) and nitrate are formed. Nitrite, however, also has toxic properties. At acid pH, nitrous acid (HNO2) is bactericidal to Escherichia coli, in association with the loss of HNO2/NO2- and the uptake of oxygen, an effect which is increased by H2O2. Under conditions in which HNO2/NO2- +/- H2O2 were ineffective, the further addition of peroxidase (myeloperoxidase [MPO], eosinophil peroxidase, lactoperoxidase) or catalase resulted in bactericidal activity and the disappearance of HNO2/NO2-. Paradoxically, HNO2/NO2- also inhibited the bactericidal activity of MPO by the formation of a complex with MPO with a shift in the absorption spectrum, and by reaction with hypochlorous acid (HOCl) (the product of the chloride-supplemented MPO-H2O2 system), with loss of the bactericidal activity of HOCl and the disappearance of both HOCl and HNO2/NO2- from the reaction mixture. Thus, HNO2/NO2-, rather than being solely an end product of RNI formation, may influence antimicrobial activity either by acting alone, with H2O2, or with H2O2 and peroxidase as a source of toxic agents, or by inhibiting the peroxidase-mediated antimicrobial systems.
Klebanoff
S J
SJ
Department of Medicine, University of Washington, Seattle 98195.
D000818:Animals; D047209:Eosinophil Peroxidase; D004926:Escherichia coli / Q000187:drug effects*; D005609:Free Radicals; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007784:Lactoperoxidase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism / Q000494:pharmacology*; D009608:Nitrous Acid / Q000378:metabolism / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism
D005609:Free Radicals; D009573:Nitrites; D006861:Hydrogen Peroxide; D047209:Eosinophil Peroxidase; D007784:Lactoperoxidase; D010544:Peroxidases; D009195:Peroxidase; D005947:Glucose; D009608:Nitrous Acid