Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2).
Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2).
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DOI：
10.1084/jem.185.9.1533
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发表时间：
1997-05-05
期刊：
影响因子：
--
通讯作者：
Rimm IJ
中科院分区：
文献类型：
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作者：
Adler H;Beland JL;Del-Pan NC;Kobzik L;Brewer JP;Martin TR;Rimm IJ
小鼠鼻内感染单纯疱疹病毒1型(HSV-1)可引起肺炎。该病的表现包括：组织性肺炎，淋巴细胞肺内流入，肺顺应性降低，存活率下降。免疫组织化学染色显示感染组小鼠肺内iNOS诱导和硝基酪氨酸抗原表达，提示一氧化氮参与肺炎的发生发展。为探讨一氧化氮在单纯疱疹病毒1型肺炎发病机制中的作用，用一氧化氮合酶活性抑制剂L精氨酸(NMMA)治疗感染小鼠，并以PBS或d-NMMA作对照。L-NMMA治疗减少了肺炎的组织学证据，并将对照组小鼠的支气管肺泡灌洗淋巴细胞数量减少到总数的四分之一。L-NMMA治疗可显著提高单纯疱疹病毒1型感染小鼠的存活率和肺顺应性。引人注目的是，尽管肺部病毒滴度高出17倍，L-NMMA介导的肺炎抑制作用还是发生了。综上所述，这些数据表明了一氧化氮在HSV-1诱导的肺炎中以前未被认识到的作用。值得注意的是，尽管肺病毒含量较高，肺炎仍受到抑制；因此，我们的数据表明，HSV-1肺炎是由于炎症反应的某些方面，而不是直接的病毒细胞病变效应。
Intranasal Herpes simplex virus type 1 (HSV-1) infection of mice caused pneumonia. Manifestations of the disease included: histological pneumonitis, pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased survival. Immunohistochemical staining demonstrated iNOS induction and the nitrotyrosine antigen in the lungs of infected, but not uninfected mice, suggesting that nitric oxide contributes to the development of pneumonia. To elucidate the role of nitric oxide in the pathogenesis of HSV-1 pneumonia, infected mice were treated either with the inhibitor of nitric oxide synthase activity, NG-monomethyl-l-arginine (l-NMMA), or, as a control, with PBS or d-NMMA. l-NMMA treatment decreased the histological evidence of pneumonia and reduced the bronchoalveolar lavage lymphocyte number to one-quarter of the total measured in control-treated mice. l-NMMA treatment significantly improved survival and pulmonary compliance of HSV-1–infected mice. Strikingly, the l-NMMA–mediated suppression of pneumonia occurred despite the presence of a 17-fold higher pulmonary viral titer. Taken together, these data demonstrated a previously unrecognized role of nitric oxide in HSV-1–induced pneumonia. Of note, suppression of pneumonia occurred despite higher pulmonary virus content; therefore, our data suggest that HSV-1 pneumonia is due to aspects of the inflammatory response rather than to direct viral cytopathic effects.