Rosen H, Klebanoff S J
J Exp Med. 1979 Jan 1;149(1):27-39. doi: 10.1084/jem.149.1.27.
The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.
乙醛 - 黄嘌呤氧化酶系统在有和没有髓过氧化物酶（MPO）及氯离子存在的情况下，已被用作中性粒细胞氧依赖性抗菌系统的模型。未添加其他成分的黄嘌呤氧化酶系统在相对较高的乙醛浓度下具有杀菌作用。超氧化物歧化酶（SOD）、过氧化氢酶、羟基自由基（OH·）清除剂甘露醇和苯甲酸盐、单线态氧（1O2）猝灭剂叠氮化物、组氨酸和1,4 - 二氮杂双环[2,2,2]辛烷（DABCO）以及嘌呤类物质黄嘌呤、次黄嘌呤和尿酸可抑制其杀菌活性。当以嘌呤作为底物时，后一种效应可能解释了黄嘌呤氧化酶系统相对较弱的杀菌活性。藤黄八叠球菌的白色、类胡萝卜素阴性突变株比黄色、类胡萝卜素阳性的亲本菌株对乙醛 - 黄嘌呤氧化酶系统更敏感。类胡萝卜素色素是有效的1O2猝灭剂。黄嘌呤氧化酶系统催化2,5 - 二苯基呋喃转化为顺式二苯甲酰乙烯，这一反应可通过1O2机制发生。这种转化受到SOD、过氧化氢酶、叠氮化物、组氨酸、DABCO、黄嘌呤、次黄嘌呤和尿酸的抑制，但仅受到甘露醇和苯甲酸盐的轻微抑制。向乙醛 - 黄嘌呤氧化酶系统中添加MPO和氯离子可大大增强杀菌活性；最低有效乙醛浓度降低100倍，细菌杀灭的速率和程度增加。添加MPO的系统的杀菌活性受到过氧化氢酶、苯甲酸盐、叠氮化物、DABCO和组氨酸的抑制，但不受SOD或甘露醇的抑制。因此，像吞噬性中性粒细胞一样能产生超氧阴离子（O·2-）和过氧化氢的乙醛 - 黄嘌呤氧化酶系统，在有和没有MPO及氯离子存在的情况下均具有杀菌作用。添加MPO的系统杀菌能力更强；然而，当没有MPO时，仍可观察到杀菌活性，这可能是由H2O2和O·2-相互作用形成OH·和1O2介导的。
