Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase

Differential host susceptibility to pulmonary infections with bacteria and fungi in mice deficient in myeloperoxidase
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DOI:
10.1086/315843
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发表时间:
2000-10-01
影响因子:
6.4
通讯作者:
Koyama, H
Koyama, H
中科院分区:
医学2区
文献类型:
--
作者:
Aratani, Y;Kura, F;Koyama, H

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髓过氧化物酶 (MPO) 位于中性粒细胞内,能够产生次氯酸,在体外具有对抗细菌和真菌的活性。然而,缺乏 MPO 的人通常是健康的。为了确定 MPO 对早期宿主防御肺部感染的体内贡献,MPO 缺陷小鼠和对照小鼠经鼻内感染各种真菌和细菌,48 小时后比较肺部残留微生物的数量。 MPO 缺陷小鼠对白色念珠菌、热带念珠菌、旭毛孢子菌和铜绿假单胞菌的细胞毒性显着降低。然而,突变小鼠对烟曲霉和肺炎克雷伯菌的清除表现出轻微但显着的延迟,并且对光滑念珠菌、新型隐球菌、金黄色葡萄球菌和肺炎链球菌具有与野生型相当的抗性水平。这些结果表明,MPO 依赖性氧化系统对于宿主防御真菌和细菌非常重要,尽管其效果因病原体种类而异。
Myeloperoxidase (MPO), which is located within neutrophils capable of producing hypochlorous acid, is active in vitro against bacteria and fungi. However, MPO-deficient persons are usually healthy. To define the in vivo contribution of MPO to early host defense against pulmonary infections, MPO-deficient and control mice were intranasally infected with various fungi and bacteria, and the number of residual microorganisms in lungs was compared 48 h later. MPO-deficient mice showed severely reduced cytotoxicity to Candida albicans, Candida tropicalis, Trichosporon asahii, and Pseudomonas aeruginosa. However, the mutant mice showed a slight but significantly delayed clearance of Aspergillus fumigatus and klebsiella pneumoniae and had comparable levels of resistance to the wild type against Candida glabrata, Cryptococcus neoformans, Staphylococcus aureus, and Streptococcus pneumoniae. These results suggest that the MPO-dependent oxidative system is important for host defense against fungi and bacteria, although the effect varies by pathogen species.