Smith K R, Veranth J M, Hu A A, Lighty J S, Aust A E
Department of Chemistry, Utah State University, Logan, Utah 84322-0300, USA.
Chem Res Toxicol. 2000 Feb;13(2):118-25. doi: 10.1021/tx9901736.
Particulate air pollution contains iron, and some of the pathological effects after inhalation may be due to radical species produced by iron-catalyzed reactions. We tested the hypothesis that iron present in coal fly ash (CFA) could induce the expression and synthesis of the inflammatory cytokine interleukin-8 (IL-8). CFA, containing as much as 14% iron, was used as a model combustion source particle. Three coal types were used to generate three size fractions enriched in particles [submicron (<1 micrometer), fine (<2.5 micrometer), or coarse (2.5-10 micrometer]), as well as the fraction of >10 micrometer. Treatment of human lung epithelial (A549) cells for 4 h with CFA from Utah enriched in <1 micrometer particles (20 microgram/cm(2)) resulted in a 2.6-fold increase in mRNA levels for IL-8. IL-8 levels were increased in the medium by as much as 8-fold when cells were treated with the fraction enriched in the smallest size Utah CFA for 24 h. IL-8 production was completely inhibited when the CFA was pretreated with the metal chelator desferrioxamine B, suggesting that a transition metal was responsible for the induction, probably iron. Treatment with a soluble form of iron, ferric ammonium citrate (FAC), mimicked the IL-8 level increase observed with CFA. There was a direct relationship, above a threshold level of bioavailable iron, between the levels of IL-8 and bioavailable iron in A549 cells treated with CFA or FAC. Further, the relationship between IL-8 and bioavailable iron for CFA was indistinguishable from that for FAC. These results strongly suggest that iron can induce IL-8 in A549 cells and that iron was the likely component of CFA that induced IL-8. CFA-induced IL-8 production was inhibited by tetramethylthiourea or dimethyl sulfoxide, suggesting that radical species were involved in the induction. These results demonstrate that iron present in CFA may be responsible for production and release of inflammatory mediators by the lung epithelium through generation of radical species and suggest that iron may contribute to the exacerbation of respiratory problems by particulate air pollution.
空气中的颗粒物污染含有铁，吸入后产生的一些病理效应可能归因于铁催化反应产生的自由基。我们验证了一个假设，即煤飞灰（CFA）中的铁可诱导炎性细胞因子白细胞介素-8（IL-8）的表达和合成。含有高达14%铁的CFA被用作模型燃烧源颗粒物。使用三种煤生成了三种富含颗粒物的粒径分级[亚微米级（<1微米）、细颗粒级（<2.5微米）或粗颗粒级（2.5 - 10微米）]，以及大于10微米的分级。用来自犹他州的富含<1微米颗粒（20微克/平方厘米）的CFA处理人肺上皮（A549）细胞4小时，导致IL-8的mRNA水平增加了2.6倍。当用富含最小粒径的犹他州CFA分级处理细胞24小时时，培养基中的IL-8水平增加了多达8倍。当CFA用金属螯合剂去铁胺B预处理时，IL-8的产生被完全抑制，这表明过渡金属是诱导的原因，可能是铁。用可溶性铁形式柠檬酸铁铵（FAC）处理，模拟了用CFA观察到的IL-8水平升高。在用CFA或FAC处理的A549细胞中，高于生物可利用铁阈值水平时，IL-8水平与生物可利用铁之间存在直接关系。此外，CFA的IL-8与生物可利用铁之间的关系与FAC的无法区分。这些结果有力地表明铁可在A549细胞中诱导IL-8，并且铁是CFA中可能诱导IL-8的成分。CFA诱导的IL-8产生被四甲基硫脲或二甲基亚砜抑制，表明自由基参与了诱导过程。这些结果表明，CFA中的铁可能通过产生自由基导致肺上皮产生和释放炎性介质，并表明铁可能导致颗粒物空气污染加剧呼吸问题。
