Reactive nitrogen intermediates and antimicrobial activity: role of nitrite

SJ Klebanoff - Free Radical Biology and Medicine, 1993 - Elsevier
SJ Klebanoff
Free Radical Biology and Medicine, 1993Elsevier
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 (NO 12−) and nitrate formed. Nitrite, however, also has toxic properties. At acid pH,
nitrous acid (HNO 2) is bactericidal to Escherichia coli, in association with the loss of HNO
2/NO 2− and the uptake of oxygen, an effect which is increased by H 2 O 2. Under conditions
in which HNO 2/NO 2−±H 2 O 2 were ineffective, the further addition of peroxidase …
Abstract
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 (NO12) and nitrate 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 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, ra being solely an end product of RNI formation, may influence antimicroboal 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.
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