Miyagi K, Kawakami K, Saito A
The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
Infect Immun. 1997 Oct;65(10):4108-13. doi: 10.1128/iai.65.10.4108-4113.1997.
We examined the contributions of reactive nitrogen and oxygen intermediates (RNI and ROI, respectively) in macrophage bactericidal activity against Burkholderia pseudomallei, the causative agent of melioidosis, in order to understand host defense mechanisms against infection caused by this bacterium. The bacteria multiplied in unstimulated murine macrophage cell line J774.1. However, a strong dose-dependent inhibition of intracellular bacterial growth was observed when gamma interferon (IFN-gamma)-activated macrophages were used. The induction of bactericidal activity correlated well with the production of nitric oxide (NO) by IFN-gamma-activated macrophages and was markedly suppressed by N(G)-monomethyl L-arginine (L-NMMA), a competitive inhibitor of NO synthesis. Superoxide dismutase (SOD) and catalase significantly inhibited macrophage bactericidal activity, and the combined addition of L-NMMA, SOD, and catalase resulted in the complete inhibition of IFN-gamma-stimulated activity. The bacteria were susceptible to the killing effects of chemically generated NO and superoxide anion in a macrophage-free system. Our results indicate that IFN-gamma-induced macrophage bactericidal activity against B. pseudomallei is mediated to a large extent by RNI killing mechanisms and to a lesser extent by ROI-dependent mechanisms.
我们研究了反应性氮和氧中间体（分别为RNI和ROI）在巨噬细胞对类鼻疽病病原体——伯克霍尔德菌的杀菌活性中的作用，以便了解宿主针对该细菌感染的防御机制。细菌在未受刺激的小鼠巨噬细胞系J774.1中繁殖。然而，当使用γ干扰素（IFN-γ）激活的巨噬细胞时，观察到细胞内细菌生长受到强烈的剂量依赖性抑制。杀菌活性的诱导与IFN-γ激活的巨噬细胞产生一氧化氮（NO）密切相关，并且被NO合成的竞争性抑制剂N(G)-单甲基-L-精氨酸（L-NMMA）显著抑制。超氧化物歧化酶（SOD）和过氧化氢酶显著抑制巨噬细胞杀菌活性，并且联合添加L-NMMA、SOD和过氧化氢酶导致IFN-γ刺激的活性完全被抑制。在无巨噬细胞系统中，细菌对化学产生的NO和超氧阴离子的杀伤作用敏感。我们的结果表明，IFN-γ诱导的巨噬细胞对类鼻疽伯克霍尔德菌的杀菌活性在很大程度上由RNI杀伤机制介导，在较小程度上由ROI依赖性机制介导。
