Prevention of influenza-induced lung injury in mice overexpressing extracellular superoxide dismutase
Prevention of influenza-induced lung injury in mice overexpressing extracellular superoxide dismutase
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DOI：
10.1152/ajplung.2001.280.1.l69
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发表时间：
2001-01-01
影响因子：
4.9
通讯作者：
Folz, RJ
中科院分区：
文献类型：
--
作者：
Suliman, HB;Ryan, LK;Folz, RJ
活性氧和氮物质如超氧化物和一氧化氮通过炎症和气道上皮细胞释放到细胞外间隙中。这些分子可能会加重流感病毒性肺炎后的肺损伤。我们假设，增强小鼠气道细胞外超氧化物歧化酶（EC SOD）的表达，将减轻流感肺炎的病理影响。我们比较了小鼠适应性香港流感A/68病毒在转基因（TG）EC SOD小鼠与非TG（野生型）同窝仔中的非致死性原发感染的致病作用。与野生型小鼠相比，EC SOD TG小鼠表现出更少的肺损伤和炎症，如通过显著减弱干扰素-γ诱导、减少支气管肺泡灌洗液中的细胞计数和总蛋白、降低肺亚硝酸盐/硝酸盐硝基酪氨酸水平以及显著减少肺病理学来测量的。这些结果表明，在肺的传导和远端气道中增强EC SOD通过改善炎症和减弱氧化应激两者来最小化流感诱导的肺损伤。
Reactive oxygen and nitrogen species such as superoxide and nitric oxide are released into the extracellular spaces by inflammatory and airway epithelial cells. These molecules may exacerbate lung injury after influenza virus pneumonia. We hypothesized that enhanced expression of extracellular superoxide dismutase (EC SOD) in mouse airways would attenuate the pathological effects of influenza pneumonia. We compared the pathogenic effects of a nonlethal primary infection with mouse-adapted Hong Kong influenza A/68 virus in transgenic (TG) EC SOD mice versus non-TG (wild-type) littermates. Compared with wild-type mice, EC SOD TG mice showed less lung injury and inflammation as measured by significant blunting of interferon-gamma induction, reduced cell count and total protein in bronchoalveolar lavage fluid, reduced levels of lung nitrite/nitrate nitrotyrosine, and markedly reduced lung pathology. These results demonstrate that enhancing EC SOD in the conducting and distal airways of the lung minimizes influenza-induced lung injury by both ameliorating inflammation and attenuating oxidative stress.