Effect of Iron Deficiency on a Murine Model of Smoke-induced Emphysema
Effect of Iron Deficiency on a Murine Model of Smoke-induced Emphysema
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缺铁对烟雾性肺气肿小鼠模型的影响
DOI：
10.1165/rcmb.2018-0239oc
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发表时间：
2020
影响因子：
6.4
通讯作者：
Shibata Yoko
中科院分区：
文献类型：
--
作者：
Sato Kento;Inoue Sumito;Igarashi Akira;Tokairin Yoshikane;Yamauchi Keiko;Kimura Tomomi;Nishiwaki Michiko;Nemoto Takako;Nakano Hiroshi;Sato Masamichi;Machida Hiroyoshi;Yang Sujeong;Minegishi Yukihiro;Furuyama Kodai;Watanabe Masafumi;Shibata Yoko
吸烟是慢性阻塞性肺疾病（COPD）的主要危险因素。吸烟易感性对于COPD的发生和发展至关重要。我们以前报道了男性吸烟者血清铁浓度与肺功能之间的关系。然而，与缺铁有关的吸烟易感性的机制尚不清楚，本研究旨在阐明这一机制。C57 BL/6雄性小鼠被喂食缺铁或正常饮食，然后暴露于香烟烟雾。在香烟烟雾暴露后进行BAL、组织学分析和肺功能测试。用铁螯合剂处理人肺泡II型上皮A549细胞。随后，将A549细胞暴露于香烟烟雾提取物。在暴露于香烟烟雾2周的小鼠中，从铁缺乏小鼠中回收的BAL液中肺泡巨噬细胞的浓度显著高于正常饮食小鼠。在缺铁小鼠中，BAL液中的IL-6和MCP-1（单核细胞趋化蛋白1）浓度较基线显著增加，但在正常饮食小鼠中没有增加。在小鼠暴露于香烟烟雾8周，病理平均线性截距，生理总肺容量，功能残气量在肺铁缺乏小鼠显着大于正常饮食小鼠。在暴露于香烟烟雾的铁缺乏小鼠肺和暴露于香烟烟雾提取物的铁螯合A549细胞中，NF-κB的磷酸化增强。缺铁加重了香烟烟雾引起的肺部炎症，这表明它可能加速COPD的发展。
Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). Smoking susceptibility is important for the onset and development of COPD. We previously reported an association between serum iron concentrations and pulmonary function in male smokers. However, the mechanism governing smoking susceptibility in relation to iron deficiency is unclear; this study aimed to elucidate this mechanism. C57BL/6 male mice were fed an iron-deficient or normal diet and then exposed to cigarette smoke. BAL, histological analysis, and pulmonary function tests were performed after cigarette smoke exposure. Human alveolar type II epithelial A549 cells were treated with an iron chelator. Subsequently, A549 cells were exposed to cigarette smoke extract. In mice exposed to cigarette smoke for 2 weeks, the concentration of alveolar macrophages in the BAL fluid recovered from iron-deficient mice was significantly higher than that in normal diet mice. IL-6 and MCP-1 (monocyte chemotactic protein 1) concentrations in the BAL fluid increased significantly from baseline in iron-deficient mice, but not in normal diet mice. In mice exposed to cigarette smoke for 8 weeks, the pathological mean linear intercepts, physiological total lung capacity, and functional residual capacity in the lungs of iron-deficient mice were significantly greater than in normal diet mice. Phosphorylation of NF-κB was enhanced in the lungs of iron-deficient mice exposed to cigarette smoke and in the iron-chelating A549 cells exposed to cigarette smoke extract. Iron deficiency exaggerated cigarette smoke–induced pulmonary inflammation, suggesting that it may accelerate COPD development.