Research on the role of NO in microbial pathogenesis

近年来，自由基分子物种在各种病毒性疾病发病机制中的重要性日益得到认识。氧自由基如超氧自由基和羟基自由基被认为是病毒发病过程中可能的致病分子。另一种简单的无机自由基一氧化氮（NO）在宿主对病毒感染的防御机制和发病机制中受到了广泛关注。NO合成途径，特别是NO合成酶（iNOS）的诱导异构体，通过诱导促炎细胞因子如干扰素-α和白细胞介素-1β在不同的病毒性疾病中表达。与NOS的其他组成型，即神经元NOS和内皮NOS相比，iNOS长时间产生过量的NO。NO的生物合成，特别是通过诱导NO合成酶（iNOS）的表达，发生在多种微生物感染中。我们对inos缺陷小鼠沙门氏菌病的研究表明，NO在沙门氏菌感染中具有重要的宿主防御功能，这不仅是因为它具有直接的抗菌作用，还可能是通过其抗凋亡作用对感染的宿主细胞具有细胞保护作用。活性氮氧化物如过氧亚硝酸盐是通过NO与超氧化物的反应在生物系统中产生的。在这些活性氮物种中，过氧亚硝酸盐及其生物学作用引起了相当大的兴趣，因为过氧亚硝酸盐引起蛋白质氨基酸残基和DNA鸟嘌呤的氧化和硝化，脂质过氧化和DNA裂解。在感染灶中形成的过氧亚硝酸盐可能是宿主防御反应中的优势氮氧化物。因此，了解NO和氧自由基生成在感染中的作用不仅可以从分子水平上了解病毒的发病机制，还可以从分子水平上了解微生物感染中宿主-病原体的相互作用。

The importance of free radical molecular species in the pathogenesis of various viral diseases has been increasingly recognized in recent years. Oxygen radicals such as superoxide and hydroxyl radical have been implicated as possible pathogenic molecules in viral disease pathogenesis. Much attention has been given to another simple inorganic radical [nitric oxide (NO)] in me host's defense mechanism and pathogenesis of virus infection. The NO synthesis pathway, in particular the inducible isoform of NO synthase (iNOS), is expressed in different viral diseases via induction of proinflammatory cytokines such as interferon-α and interleukin-1β. iNOS produces an excessive amount of NO for a long time compared with other constitutive isoforms of NOS, i.e., neuronal NOS and endothelial NOS. NO biosynthesis, particularly through expression of an inducible NO synthase (iNOS), occurs in a variety of microbial infections. Our work on murine salmonellosis in iNOS-deficient mice indicated that NO has significant host defense functions in Salmonella infections not only because of its direct antimicrobial effect but also via cytoprotective actions for infected host cells, possibly through its antiapoptotic effect. Reactive nitrogen oxide species such as peroxynitrite are produced in biological systems through the reaction of NO with superoxide. Among these reactive nitrogen species, peroxynitrite and its biological actions are of considerable interest in that peroxynitrite causes oxidation and nitration of amino acid residues of proteins and guanine of DNA, lipid peroxidation, and DNA cleavage. Peroxynitrite thus formed in infectious foci may be a dominant nitrogen oxide species during the host's defense reactions. Thus, understanding of the role of NO and oxygen radical generation in infections will provide insight into not only viral pathogenesis but also the host-pathogen interaction in microbial infections at a molecular level.