Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-κB activation and IL-8 mRNA expression in guinea pigs in vivo
Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-κB activation and IL-8 mRNA expression in guinea pigs in vivo
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DOI：
10.1165/ajrcmb.20.2.3305
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发表时间：
1999-02-01
影响因子：
6.4
通讯作者：
Okubo, T
中科院分区：
文献类型：
--
作者：
Nishikawa, M;Kakemizu, N;Okubo, T
我们研究的假设，超氧化物介导的中性粒细胞浸润的气道，通过核因子（NF）-κ B和白细胞介素-8（IL-8）急性暴露于香烟烟雾（CS）在体内。将雄性Hartley品系豚鼠暴露于空气或20喷CS，并在暴露后5 h处死。支气管肺泡灌洗液的分类细胞计数和特异性髓过氧化物酶测定表明，急性暴露于CS引起中性粒细胞积聚的气道和实质，分别。急性暴露于CS增加了肺中NF-κ B的DNA结合活性。急性暴露于CS也增加了IL-8信使RNA（mRNA）在肺中的表达。用重组人超氧化物歧化酶（rhSOD）气雾剂预处理豚鼠可减少CS诱导的中性粒细胞在气道中的蓄积。rhSOD气雾剂预处理也抑制了NF-κ B B的活化和IL-8 mRNA表达的增加。急性染毒后肺泡巨噬细胞核内p65和p50免疫反应阳性。IL-8 mRNA表达的信号被证明在肺泡腔后急性暴露于CS。在气道上皮中未观察到明显的p65和p50免疫反应性，也未观察到IL-8 mRNA信号。这些观察结果表明，急性暴露于CS启动超氧化物依赖性机制，通过NF-κ B活化和IL-8 mRNA表达，产生中性粒细胞浸润到体内气道。肺泡巨噬细胞是CS急性暴露后NF-κ B B活化和IL-8 mRNA表达的一个潜在来源。
We examined the hypothesis that superoxide mediates infiltration of neutrophils to the airways through nuclear factor (NF)-kappa B and interleukin-8 (IL-8) after acute exposure to cigarette smoke (CS) in vivo . Male Hartley strain guinea pigs were exposed to air or 20 puffs of CS and killed 5 h after the exposure. The differential cell count of bronchoalveolar lavage fluid and specific myeloperoxidase enzyme assay demonstrated that acute exposure to CS caused neutrophil accumulation to the airways and parenchyma, respectively. Acute exposure to CS increased DNA-binding activity of NF-kappa B in the lung. Acute exposure to CS also increased IL-8 messenger RNA (mRNA) expression in the lung. Pretreatment of guinea pigs with recombinant human superoxide dismutase (rhSOD) aerosols reduced the CS-induced neutrophil accumulation to the airways. Both activation of NF-kappa B and increased IL-8 mRNA expression were also inhibited by the pretreatment of rhSOD aerosols. Strong immunoreactivities for p65 and p50 were detected in the nuclei of alveolar macrophages after acute exposure to CS. The signal for IL-8 mRNA expression was demonstrated in the alveolar space after acute exposure to CS. Neither significant immunoreactivities for p65 and p50 nor IL-8 mRNA signals were observed in airway epithelium. These observations suggest that acute exposure to CS initiates superoxide-dependent mechanism that, through NF-kappa B activation and IL-8 mRNA expression, produces infiltration of neutrophils to the airways in vivo. It was also suggested that the alveolar macrophage is one potential source of NF-kappa B activation and IL-8 mRNA expression after acute exposure to CS.