Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase
Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase
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DOI：
10.1016/s1074-7613(00)80004-7
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发表时间：
1999-01-01
期刊：
影响因子：
32.4
通讯作者：
Nathan, C
中科院分区：
文献类型：
--
作者：
Shiloh, MU;MacMicking, JD;Nathan, C
巨噬细胞的两种遗传机制是通过吞噬细胞氧化酶（phox）产生活性氧中间体和通过诱导型一氧化氮合酶（NOS2）产生活性氮中间体。两种酶(gp91（phox-/-)/NOS2(-/-)）双重缺乏的小鼠即使在使用抗生素的特定无病原体条件下饲养，也会形成含有共生生物（主要是肠道细菌）的大量脓肿。亲本菌株均未显示出这种感染。因此，phox和NOS2似乎在提供对本地细菌的抗性方面相互弥补了彼此的不足，没有其他途径能完全做到这一点。gp91(phox-/-) NOS2（-/-）小鼠巨噬细胞不能杀伤李斯特菌。巨噬细胞对鼠伤寒沙门氏菌、大肠杆菌和减毒李斯特菌的杀伤作用明显减弱，这表明巨噬细胞的抗菌活性存在一种不依赖于phox和NOS2的机制。
The two genetically established antimicrobial mechanisms of macrophages are production of reactive oxygen intermediates by phagocyte oxidase (phox) and reactive nitrogen intermediates by inducible nitric oxide synthase (NOS2). Mice doubly deficient in both enzymes (gp91(phox-/-)/NOS2(-/-)) formed massive abscesses containing commensal organisms, mostly enteric bacteria, even when reared under specific pathogen-free conditions with antibiotics. Neither parental strain showed such infections. Thus, phox and NOS2 appear to compensate for each other's deficiency in providing resistance to indigenous bacteria, and no other pathway does so fully. Macrophages from gp91(phox-/-) NOS2(-/-)mice could not kill virulent Listeria. Their killing of S. typhimurium, E. coli, and attenuated Listeria was markedly diminished but demonstrable, establishing the existence of a mechanism of macrophage antibacterial activity independent of phox and NOS2.