Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro
Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro
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DOI：
10.1016/j.taap.2003.11.021
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发表时间：
2004-04-01
影响因子：
3.8
通讯作者：
Donaldson, K
中科院分区：
文献类型：
--
作者：
McNeilly, JD;Heal, MR;Donaldson, K
流行病学研究一致报告，暴露于高浓度富含金属的焊接烟雾中的焊工患支气管炎、金属烟雾热（MFF）和慢性肺炎等呼吸系统疾病的发生率较高。在这里，我们研究了三种不同的富含金属的焊接烟雾的分子毒理学：NIMROD 182， NIMROD c276和COBSTEL 6。通过将人类11型肺泡上皮细胞系（A549）暴露于整个焊接烟雾，烟雾的可溶性提取物或“洗涤”颗粒来确定烟雾的体外毒性。在剂量> ~ 63马克毫升（-1）时，所有烟雾对A549细胞均有显著毒性（TD分别为50、42、25和12马克毫升（-1））。NIMROD c276和COBSTEL 6烟雾在第6小时和第24小时增加了IL-8 mRNA和蛋白质的水平，就像单独的可溶性部分一样，而使用螯合珠对可溶性部分的金属螯合则减弱了这种效果。这三种烟雾的可溶部分在暴露于A549细胞2小时后引起细胞内谷胱甘肽的快速消耗，并在24小时内反弹增加。此外，根据DCFH荧光测定，镍基烟雾NIMROD 182和NIMROD c276在2小时后诱导A549细胞产生显著的活性氧（ROS）。ICP分析证实，过渡金属浓度在每个烟雾的整体和可溶部分（以Cr为主）中相似，但在洗涤颗粒和螯合部分中明显较少。这些结果支持了一种假设，即焊接烟尘颗粒的促炎反应是由可溶性过渡金属成分通过氧化应激机制介导的。(C) 2004爱思唯尔公司版权所有。
Epidemiological studies have consistently reported a higher incidence of respiratory illnesses such as bronchitis, metal fume fever (MFF), and chronic pneumonitis among welders exposed to high concentrations of metal-enriched welding fumes. Here, we studied the molecular toxicology of three different metal-rich welding fumes: NIMROD 182, NIMROD c276, and COBSTEL 6. Fume toxicity in vitro was determined by exposing human type 11 alveolar epithelial cell line (A549) to whole welding fume, a soluble extract of fume or the "washed" particulate. All whole fumes were significantly toxic to A549 cells at doses >63 mug ml(-1) (TD 50; 42, 25, and 12 mug ml(-1), respectively). NIMROD c276 and COBSTEL 6 fumes increased levels of IL-8 mRNA and protein at 6 h and protein at 24 h, as did the soluble fraction alone, whereas metal chelation of the soluble fraction using chelex beads attenuated the effect. The soluble fraction of all three fumes caused a rapid depletion in intracellular glutathione following 2-h exposure with a rebound increase by 24 h. In addition, both nickel based fumes, NIMROD 182 and NIMROD c276, induced significant reactive oxygen species (ROS) production in A549 cells after 2 h as determined by DCFH fluorescence. ICP analysis confirmed that transition metal concentrations were similar in the whole and soluble fractions of each fume (dominated by Cr), but significantly less in both the washed particles and chelated fractions. These results support the hypothesis that the enhanced pro-inflammatory responses of welding fume particulates are mediated by soluble transition metal components via an oxidative stress mechanism. (C) 2004 Elsevier Inc. All rights reserved.