title: Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro.
abstract: 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 II 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 microg ml(-1) (TD 50; 42, 25, and 12 microg 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.
authors.affiliation: Respiratory Medicine Unit, ELEGI/Colt Laboratories, University of Edinburgh, Edinburgh EH8 9AG, UK.
authors.forename: Jane D
authors.initials: JD
authors.lastname: McNeilly
authors.forename: Mathew R
authors.initials: MR
authors.lastname: Heal
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Beverland
authors.forename: Alan
authors.initials: A
authors.lastname: Howe
authors.forename: Mark D
authors.initials: MD
authors.lastname: Gibson
authors.forename: Leon R
authors.initials: LR
authors.lastname: Hibbs
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.forename: Ken
authors.initials: K
authors.lastname: Donaldson
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis; D019216:Metals, Heavy / Q000633:toxicity*; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D014896:Welding
chemical_list: D000395:Air Pollutants, Occupational; D018836:Inflammation Mediators; D016209:Interleukin-8; D019216:Metals, Heavy; D012333:RNA, Messenger; D017382:Reactive Oxygen Species