Comparison of the roles of reactive oxygen and nitrogen intermediates in the host response to Mycobacterium tuberculosis using transgenic mice
Comparison of the roles of reactive oxygen and nitrogen intermediates in the host response to Mycobacterium tuberculosis using transgenic mice
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DOI：
10.1016/s0962-8479(97)90004-6
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发表时间：
1997-01-01
期刊：
影响因子：
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通讯作者：
Krahenbuhl, JL
中科院分区：
文献类型：
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作者：
Adams, LB;Dinauer, MC;Krahenbuhl, JL
目的：研究活性氧中间体（ROI）和活性氮中间体（RNI）在结核分枝杆菌感染中的作用。结核病感染（i. v.）在B6对照和两种基因敲除（KO）小鼠中比较。具有吞噬细胞氧化酶细胞色素B的gp 91（phox）亚基的非功能性等位基因的X-CGD小鼠不能产生ROI，而iNOS KO小鼠缺乏功能性诱导型一氧化氮合酶（iNOS）基因，不能产生RNI。M.与B6小鼠相比，X-CGD小鼠的肺中结核生长显著增强，但脾脏和肝脏中的结核生长得到控制。在iNOS KO小鼠中，M.与B6小鼠相比，结核病在脾脏中的生长加剧，但在肺中并不显著，直到感染后期（第60天）。在体外，X-CGD肺泡和腹腔巨噬细胞（M Phi）不产生ROI，但产生RNI并抑制M的生长。当用干扰素γ激活时，iNOS KO M Phi产生ROI，但不能产生RNI，并且不能科普M。结核病在体外被激活时。抑制M.结论：这些KO小鼠品系证明ROI和RNI在抗M.结核病，并应被证明对免疫调节和补偿机制的研究有用。
Objective: To study the role of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) in host response to Mycobacterium tuberculosis.Design: M. tuberculosis infection (i.v.) was compared in B6 control and two strains of knockout (KO) mice. X-CGD mice with a nonfunctional allele for the gp91(phox) subunit of the phagocyte oxidase cytochrome b are unable to produce ROI whereas iNOS KO mice lack a functional inducible nitric oxide synthase (iNOS) gene and fail to make RNI.Results. M. tuberculosis growth was markedly enhanced in the lungs of X-CGD mice compared to B6 mice, but was controlled in the spleen and liver. In iNOS KO mice, M. tuberculosis growth was exacerbated in the spleen, but was unremarkable in the lungs compared to B6 mice until later (Day 60) in the infection. In vitro, X-CGD alveolar and peritoneal macrophages (M Phi) produced no ROI, but did produce RNI and inhibited growth of M. tuberculosis when activated with interferon gamma. iNOS KO M Phi produced ROI, but failed to produce RNI and could not cope with M. tuberculosis in vitro when activated. The inhibition of M. tuberculosis growth observed in activated B6 and X-CGD M Phi) was reversed in the presence of aminoguanidine.Conclusion: These KO mouse strains demonstrate the relative potent effects of ROI and RNI in resistance to M. tuberculosis and should prove useful for the study of regulatory and compensatory mechanisms of immunity.