Fakhrzadeh Ladan, Laskin Jeffrey D, Gardner Carol R, Laskin Debra L
Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, NJ, USA.
Am J Respir Cell Mol Biol. 2004 Mar;30(3):280-7. doi: 10.1165/rcmb.2003-0044OC. Epub 2003 Jul 10.
Reactive oxygen intermediates have been implicated in lung injury induced by inhaled irritants. The present studies used mice overexpressing Cu/Zn-superoxide dismutase (SOD+/+) to analyze their role in ozone-induced lung inflammation and cytotoxicity. Treatment of wild-type mice with ozone (0.8 ppm, 3 h) resulted in increased bronchoalveolar lavage fluid protein, which was maximal after 24-48 h. Significant increases in lung macrophages and 4-hydroxyalkenals were also observed. In contrast, bronchoalveolar lavage fluid protein and macrophage content and 4-hydroxyalkenals were at control levels in ozone-treated SOD+/+ mice. There was also no evidence of peroxynitrite-mediated lung damage, demonstrating that SOD+/+ mice are resistant to ozone toxicity. Whereas alveolar macrophages from wild-type mice produced increased amounts of nitric oxide and expressed more inducible nitric oxide synthase, phospholipase A(2), and tumor necrosis factor-alpha after ozone inhalation, this was not evident in cells from SOD+/+ mice. Ozone-induced decreases in interleukin-10 were also not observed. In wild-type mice, ozone inhalation resulted in activation of nuclear factor-kappaB, which regulates proinflammatory gene activity. This response was significantly reduced in SOD+/+ mice. These data demonstrate that antioxidant enzymes play a critical role in ozone-induced tissue injury and in inflammatory mediator production.
活性氧中间体与吸入性刺激物所致的肺损伤有关。本研究使用过表达铜/锌超氧化物歧化酶的小鼠（SOD+/+）来分析其在臭氧诱导的肺部炎症和细胞毒性中的作用。用臭氧（0.8 ppm，3小时）处理野生型小鼠后，支气管肺泡灌洗液中的蛋白质增加，在24 - 48小时后达到最大值。肺巨噬细胞和4 - 羟基烯醛也显著增加。相比之下，在经臭氧处理的SOD+/+小鼠中，支气管肺泡灌洗液中的蛋白质、巨噬细胞含量和4 - 羟基烯醛处于对照水平。也没有证据表明存在过氧亚硝酸盐介导的肺损伤，这表明SOD+/+小鼠对臭氧毒性具有抗性。吸入臭氧后，野生型小鼠的肺泡巨噬细胞产生的一氧化氮量增加，并且诱导型一氧化氮合酶、磷脂酶A(2)和肿瘤坏死因子 - α的表达更多，但在SOD+/+小鼠的细胞中并不明显。也未观察到臭氧诱导的白细胞介素 - 10减少。在野生型小鼠中，吸入臭氧会导致核因子 - κB激活，该因子调节促炎基因活性。在SOD+/+小鼠中，这种反应显著降低。这些数据表明抗氧化酶在臭氧诱导的组织损伤和炎症介质产生中起关键作用。
