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首页> 外文期刊>Infection and immunity >The Intracellular Environment of Human Macrophages That Produce Nitric Oxide Promotes Growth of Mycobacteria
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The Intracellular Environment of Human Macrophages That Produce Nitric Oxide Promotes Growth of Mycobacteria

机译：产生一氧化氮的人类巨噬细胞的细胞内环境促进分枝杆菌的生长

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Nitric oxide (NO) is a diffusible radical gas produced from the activity of nitric oxide synthase (NOS). NOS activity in murine macrophages has a protective role against mycobacteria through generation of reactive nitrogen intermediates (RNIs). However, the production of NO by human macrophages has remained unclear due to the lack of sensitive reagents to detect NO directly. The purpose of this study was to investigate NO production and the consequence to mycobacteria in primary human macrophages. We found that Mycobacterium bovis BCG or Mycobacterium tuberculosis infection of human macrophages induced expression of NOS2 and NOS3 that resulted in detectable production of NO. Treatment with gamma interferon (IFN-γ), l-arginine, and tetrahydrobiopterin enhanced expression of NOS2 and NOS3 isoforms, as well as NO production. Both of these enzymes were shown to contribute to NO production. The maximal level of NO produced by human macrophages was not bactericidal or bacteriostatic to M. tuberculosis or BCG. The number of viable mycobacteria was increased in macrophages that produced NO, and this requires expression of nitrate reductase. An narG mutant of M. tuberculosis persisted but was unable to grow in human macrophages. Taken together, these data (i) enhance our understanding of primary human macrophage potential to produce NO, (ii) demonstrate that the level of RNIs produced in response to IFN-γ in vitro is not sufficient to limit intracellular mycobacterial growth, and (iii) suggest that mycobacteria may use RNIs to enhance their survival in human macrophages.
机译：一氧化氮（NO）是一氧化氮合酶（NOS）的活性产生的可扩散自由基气体。鼠巨噬细胞中的NOS活性通过生成反应性氮中间体（RNI）而对分枝杆菌具有保护作用。然而，由于缺乏直接检测NO的灵敏试剂，人类巨噬细胞对NO的产生仍不清楚。本研究的目的是调查原代人巨噬细胞中NO的产生及其对分枝杆菌的影响。我们发现人巨噬细胞的牛分枝杆菌BCG或结核分枝杆菌感染诱导NOS2和NOS3的表达，导致可检测到的NO的产生。用γ-干扰素（IFN-γ），1-精氨酸和四氢生物蝶呤处理可增强NOS2和NOS3同工型的表达以及NO的产生。已显示这两种酶均有助于NO的产生。人巨噬细胞产生的最大NO含量对结核分枝杆菌或BCG而言没有杀菌作用。在产生NO的巨噬细胞中，活的分枝杆菌的数量增加了，这需要表达硝酸还原酶。结核分枝杆菌的 narG 突变体持续存在，但无法在人类巨噬细胞中生长。综上所述，这些数据（i）增强了我们对人类主要巨噬细胞产生NO潜能的理解;（ii）表明了对IFN-γ体外的响应所产生的RNIs的水平不足以限制胞内分枝杆菌的生长，以及（iii）表明分枝杆菌可以利用RNI来提高其在人类巨噬细胞中的存活率。

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