Particulate Matter in Cigarette Smoke Alters Iron Homeostasis to Produce a Biological Effect

Particulate Matter in Cigarette Smoke Alters Iron Homeostasis to Produce a Biological Effect
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DOI:
10.1164/rccm.200802-334oc
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发表时间:
2008-12-01
影响因子:
24.7
通讯作者:
Pinkerton, Kent E.
Pinkerton, Kent E.
中科院分区:
医学1区
文献类型:
--
作者:
Ghio, Andrew J.;Hilborn, Elizabeth D.;Pinkerton, Kent E.

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原理吸烟后的肺损伤与颗粒滞留有关。铁随着这些颗粒的沉积而积累。目的:我们测试了以下假设:(1)吸烟后的损伤与暴露于香烟烟雾的颗粒部分相关,(2)这些颗粒改变铁稳态,引发金属积累,(3)铁稳态的这种改变影响氧化应激和炎症。方法:将大鼠和人呼吸道上皮细胞暴露于香烟烟雾、过滤香烟烟雾,和香烟烟雾冷凝物(烟雾的颗粒部分),以及铁稳态,氧化应激和炎症损伤的指标进行了测定。在非吸烟者和smokers. Measures和主要结果:大鼠暴露于香烟烟雾后,灌洗液中的铁和铁蛋白浓度增加,血清铁蛋白水平,肺和肝组织中的非血红素铁浓度均增加。灌洗抗坏血酸浓度降低,支持氧化应激。在过滤香烟烟雾以去除颗粒物后,这些变化中的大多数都被逆转了。培养的呼吸道上皮细胞暴露于香烟烟雾冷凝物引起类似的铁积累,金属依赖性氧化应激,并增加IL-8的释放。健康吸烟者和吸烟慢性阻塞性肺疾病患者的灌洗液样本显示,相对于健康非吸烟者,铁和铁蛋白的浓度升高。灌洗抗坏血酸减少吸烟。吸烟者血清铁和铁蛋白水平增加,支持香烟烟雾暴露后,这种金属的全身积累。结论:我们得出结论,香烟烟雾颗粒改变铁稳态,在肺和全身。
Rationale Lung injury after cigarette smoking is related to particle retention. Iron accumulates with the deposition of these particles. Objectives: We tested the postulate that (1) injury after smoking correlates with exposure to the particulate fraction of cigarette smoke, (2) these particles alter iron homeostasis, triggering metal accumulation, and (3) this alteration in iron homeostasis affects oxidative stress and inflammation.Methods: Rats and human respiratory epithelial cells were exposed to cigarette smoke, filtered cigarette smoke, and cigarette smoke condensate (the particulate fraction of smoke), and indices of iron homeostasis, oxidative stress, and inflammatory injury were determined. Comparable measures were also evaluated in nonsmokers and smokers.Measurements and Main Results: After exposure of rats to cigarette smoke, increased lavage concentrations of iron and ferritin, serum ferritin levels, and nonheme iron concentrations in the lung and liver tissue all increased. Lavage ascorbate concentrations were decreased, supporting an oxidative stress. After filtering of the cigarette smoke to remove particles, most of these changes were reversed. Exposure of cultured respiratory epithelial cells to cigarette smoke condensate caused a similar accumulation of iron, metal-dependent oxidative stress, and increased IL-8 release. Lavage samples in healthy smokers and smoking patients with chronic obstructive pulmonary disease revealed elevated concentrations of both iron and ferritin relative to healthy nonsmokers. Lavage ascorbate decreased with cigarette smoking. Serum iron and ferritin levels among smokers were increased, supporting systemic accumulation of this metal after cigarette smoke exposure.Conclusions: We conclude that cigarette smoke particles alter iron homeostasis, both in the lung and systemically.