Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans
Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans
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DOI：
10.1086/340635
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发表时间：
2002-06-15
影响因子：
6.4
通讯作者：
Koyama, H
中科院分区：
文献类型：
--
作者：
Aratani, Y;Kura, F;Koyama, H
髓过氧化物酶（MPO）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶产生的氧代谢产物有助于吞噬细胞杀死微生物。为了比较这2种酶在宿主防御中的重要性，用3种不同剂量的白色念珠菌腹腔感染MPO缺陷型（MPO-/-）小鼠和慢性肉芽肿病NADPH氧化酶缺陷型（CGD）小鼠，并分析其感染严重程度。CGD小鼠死亡率增加，并以剂量依赖性方式表现出组织真菌负荷增加，而正常小鼠则无症状。有趣的是，在最高剂量下，MPO-/-小鼠的死亡率与CGD小鼠相当，但在最低剂量下，与正常小鼠相同。在中等剂量下，在感染第6天，传播到MPO-/-小鼠的各种器官中的真菌数量与CGD小鼠相当，但在第14天显著较低。这些结果表明，MPO和NADPH氧化酶是同样重要的早期宿主防御对一个大的接种念珠菌。
Oxygen metabolites generated by myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase contribute to microbial killing by phagocytes. To compare the importance of the 2 enzymes for host defense, MPO-deficient (MPO-/-) mice and NADPH-oxidase- deficient mice with chronic granulomatous disease (CGD mice) were intraperitoneally infected with 3 different doses of Candida albicans, and their infection severity was analyzed. CGD mice had increased mortality and exhibited increased tissue fungal burden in a dose-dependent manner, whereas normal mice showed no symptoms. Of interest, at the highest dose, the mortality of MPO-/- mice was comparable to that of CGD mice, but at the lowest dose, it was the same as that of normal mice. At the middle dose, the number of fungi disseminated into various organs of the MPO-/- mice was comparable to that of the CGD mice at day 6 of infection, but it was significantly lower at day 14. These results suggest that MPO and NADPH-oxidase are equally important for early host defense against a large inoculum of Candida.