Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections with Candida albicans and Aspergillus fumigatus
Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections with Candida albicans and Aspergillus fumigatus
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DOI：
10.1080/mmy.40.6.557.563
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发表时间：
2002-12-01
期刊：
影响因子：
2.9
通讯作者：
Koyama, H
中科院分区：
文献类型：
--
作者：
Aratani, Y;Kura, F;Koyama, H
由吞噬细胞产生的氧化产物已知是针对杀死入侵微生物的重要宿主防御机制。在基因工程小鼠中直接比较了两种主要的氧化剂产生酶，髓过氧化物酶（MPO）和NADPH氧化酶在体内杀真菌作用中的重要性。与正常小鼠相比，MPO-/-和NADPH氧化酶缺陷（X连锁慢性肉芽肿病[X-CGD]）小鼠对白色念珠菌和烟曲霉肺部感染的易感性增加，X-CGD小鼠的存活率低于MPO-/-小鼠。X-CGD小鼠死亡率的增加与前6天内其器官中真菌生长增加10至100倍有关。这些结果表明，由NADPH氧化酶产生的超氧化物（O-2（-））比由MPO产生的次氯酸（HOCl）更重要，虽然这两种氧化产物显然有助于宿主防御肺部感染这些真菌。我们还观察到MPO-/-/X-CGD双基因敲除小鼠与X-CGD小鼠对C. albicans和A.烟曲霉，表明MPO，是。在没有NADPH氧化酶的情况下不能在宿主防御中发挥作用。这有力地表明，过氧化氢，HOCl的前体，是完全来自O-2（-）由NADPH氧化酶产生。
Generation of oxidative products by phagocytic cells is known to be an important host defense mechanism directed toward killing of invading microorganisms. The importance of two major oxidant-producing enzymes, myeloperoxidase (MPO) and NADPH-oxidase, in in vivo fungicidal action was directly compared in genetically engineered mice. Both MPO-deficient (MPO-/-) and NADPH-oxidase-deficient (X-linked chronic granulomatous disease [X-CGD]) mice showed increased susceptibility to pulmonary infections with Candida albicans and Aspergillus fumigatus compared with normal mice, and the X-CGD mice exhibited shorter survivals than MPO-/- mice. This increased mortality of X-CGD mice was associated with a 10- to 100-fold increased outgrowth of the fungi in their organs during the first 6 days. These results suggest that superoxide (O-2(-)) produced by NADPH-oxidase is more important than hypochlorous acid (HOCl) produced by MPO, although both oxidative products obviously contribute to the host defense against pulmonary-infection with those fungi. We also observed that MPO-/-/X-CGD double knockout mice showed comparable levels of susceptibility to the X-CGD mice against C. albicans and A. fumigatus, indicating that MPO, is. unable to play a role in host defense in the absence of NADPH-oxidase. This strongly suggests that hydrogen peroxide, the precursor of HOCl, is solely derived from O-2(-) produced by NADPH-oxidase.