Calderon R A, Shennan G I
Immunology. 1987 Jul;61(3):283-8.
Two dermatophyte strains, Trichophyton quinckeanum and Trichophyton rubrum, were highly susceptible to in vitro killing by components of the H2O2-peroxidase-halide system. Both strains were, however, resistant to relatively high concentrations of reagent H2O2 or H2O2 enzymatically generated by glucose and glucose oxidase, KI, or lactoperoxidase (LPO) alone. Resistance to hydrogen peroxidase killing was found to be in part due to the presence of endogenous catalase in the fungi; susceptibility was increased by pretreatment of the fungi with a catalase inhibitor. Kinetic studies using small quantities of reagent or enzymatically generated H2O2 and LPO-KI showed that the system was lethal for both fungal strains within 1 min. Furthermore, using the glucose-glucose oxidase-LPO-KI system, it was shown that catalase, superoxide dismutase and histidine scavengers of H2O2, superoxide anion and singlet oxygen, respectively, prevented the killing of fungus, whereas scavengers of hydroxyl radicals such as benzoate and mannitol had no effect. T. quinckeanum was found to contain large quantities of superoxide anion, as judged by the nitroblue-tetrazolium test. Consequently, the xanthine (or hypoxanthine) and xanthine oxidase system in which the main product is superoxide anion had no toxic effect on the fungus. The high sensitivity of dermatophytes to killing by the H2O2-peroxidase-halide system active in polymorphonuclear neutrophils and macrophages may account in part for fungal toxicity in vivo.
两种皮肤癣菌菌株,即昆克氏毛癣菌和红色毛癣菌,对过氧化氢 - 过氧化物酶 - 卤化物系统的成分在体外杀灭作用高度敏感。然而,这两种菌株对相对高浓度的试剂过氧化氢或由葡萄糖和葡萄糖氧化酶、碘化钾或单独的乳过氧化物酶(LPO)酶促产生的过氧化氢具有抗性。发现对过氧化氢杀灭的抗性部分归因于真菌中内源性过氧化氢酶的存在;用过氧化氢酶抑制剂预处理真菌可增加其敏感性。使用少量试剂或酶促产生的过氧化氢以及LPO - KI进行的动力学研究表明,该系统在1分钟内对两种真菌菌株均具有致死性。此外,使用葡萄糖 - 葡萄糖氧化酶 - LPO - KI系统表明,过氧化氢酶、超氧化物歧化酶以及分别针对过氧化氢、超氧阴离子和单线态氧的组氨酸清除剂可阻止真菌被杀死,而诸如苯甲酸盐和甘露醇等羟基自由基清除剂则没有效果。通过硝基蓝四氮唑试验判断,发现昆克氏毛癣菌含有大量超氧阴离子。因此,以超氧阴离子为主要产物的黄嘌呤(或次黄嘌呤)和黄嘌呤氧化酶系统对该真菌没有毒性作用。皮肤癣菌对在多形核中性粒细胞和巨噬细胞中起作用的过氧化氢 - 过氧化物酶 - 卤化物系统杀灭的高敏感性可能部分解释了真菌在体内的毒性。