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.