Klebanoff S J
Department of Medicine, University of Washington, Seattle 98195.
Free Radic Biol Med. 1993 Apr;14(4):351-60. doi: 10.1016/0891-5849(93)90084-8.
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.
反应性氮中间产物（RNI）一氧化氮（NO·）由一氧化氮合酶作用于L-精氨酸生成，经过产生其他有毒中间产物的二次反应后，生成亚硝酸盐（NO2-）和硝酸盐。然而，亚硝酸盐也具有毒性。在酸性pH条件下，亚硝酸（HNO2）对大肠杆菌具有杀菌作用，这与HNO2/NO2-的减少及氧气的摄取有关，H2O2可增强这种作用。在HNO2/NO2- +/- H2O2无效的条件下，进一步添加过氧化物酶（髓过氧化物酶[MPO]、嗜酸性粒细胞过氧化物酶、乳过氧化物酶）或过氧化氢酶会导致杀菌活性以及HNO2/NO2-的消失。矛盾的是，HNO2/NO2-还会通过与MPO形成复合物并导致吸收光谱发生变化，以及与次氯酸（HOCl）（氯化物补充的MPO-H2O2系统的产物）反应，使HOCl的杀菌活性丧失且反应混合物中HOCl和HNO2/NO2-均消失，从而抑制MPO的杀菌活性。因此，HNO2/NO2-并非仅仅是RNI形成的终产物，它可能通过单独作用、与H2O2共同作用、与H2O2及过氧化物酶作为有毒剂来源共同作用，或通过抑制过氧化物酶介导的抗菌系统来影响抗菌活性。
