Key Points Cigarette Smoke reduces hepcidin levels in the lung, plasma, and urine of mice. Cigarette smoke inhibits hepcidin production by murine AMs. AMs from smokers and individuals with COPD have higher ferroportin. Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease associated with cigarette smoking. Alterations in local lung and systemic iron regulation are associated with disease progression and pathogenesis. Hepcidin, an iron regulatory peptide hormone, is altered in subjects with COPD; however, the molecular role of hepcidin in COPD pathogenesis remains to be determined. In this study, using a murine model of smoke-induced COPD, we demonstrate that lung and circulating hepcidin levels are inhibited by cigarette smoke. We show that cigarette smoke exposure increases erythropoietin and bone marrow–derived erythroferrone and leads to expanded but inefficient erythropoiesis in murine bone marrow and an increase in ferroportin on alveolar macrophages (AMs). AMs from smokers and subjects with COPD display increased expression of ferroportin as well as hepcidin. Notably, murine AMs exposed to smoke fail to increase hepcidin in response to Gram-negative or Gram-positive infection. Loss of hepcidin in vivo results in blunted functional responses of AMs and exaggerated responses to Streptococcus pneumoniae infection.

中文翻译：

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铁调素对肺泡巨噬细胞功能至关重要，并在小鼠慢性阻塞性肺疾病模型中被烟雾破坏

要点 香烟烟雾会降低小鼠肺、血浆和尿液中的铁调素水平。香烟烟雾抑制小鼠 AMs 产生铁调素。吸烟者和 COPD 患者的 AM 具有更高的铁转运蛋白。慢性阻塞性肺疾病 (COPD) 是一种与吸烟有关的使人衰弱的肺部疾病。局部肺和全身铁调节的改变与疾病进展和发病机制有关。铁调素是一种铁调节肽激素，在 COPD 受试者中发生改变；然而，铁调素在 COPD 发病机制中的分子作用仍有待确定。在这项研究中，我们使用烟雾诱导的 COPD 小鼠模型，证明肺和循环铁调素水平受到香烟烟雾的抑制。我们表明，香烟烟雾暴露会增加促红细胞生成素和骨髓衍生的促红细胞生成素，并导致小鼠骨髓中红细胞生成扩大但效率低下，以及肺泡巨噬细胞 (AMs) 上的铁转运蛋白增加。来自吸烟者和 COPD 受试者的 AM 显示铁转运蛋白和铁调素的表达增加。值得注意的是，暴露于烟雾中的小鼠 AMs 未能增加响应革兰氏阴性或革兰氏阳性感染的铁调素。体内铁调素的丢失导致 AMs 的功能反应迟钝和对肺炎链球菌感染的反应过度。暴露于烟雾的小鼠 AMs 无法增加铁调素以响应革兰氏阴性或革兰氏阳性感染。体内铁调素的丢失导致 AMs 的功能反应迟钝和对肺炎链球菌感染的反应过度。暴露于烟雾中的小鼠 AMs 未能增加对革兰氏阴性或革兰氏阳性感染的铁调素。体内铁调素的丢失导致 AMs 的功能反应迟钝和对肺炎链球菌感染的反应过度。