Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro.

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.

[1]  M. Costa,et al.  Nickel induces increased oxidants in intact cultured mammalian cells as detected by dichlorofluorescein fluorescence. , 1993, Toxicology and applied pharmacology.

[2]  Kent D. Sugden,et al.  Hypervalent chromium mimics reactive oxygen species as measured by the oxidant-sensitive dyes 2',7'-dichlorofluorescin and dihydrorhodamine. , 1998, Chemical research in toxicology.

[3]  P. Harber,et al.  Current issues in occupational lung disease. , 1988, The American review of respiratory disease.

[4]  F. Tietze.  Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. , 1969, Analytical biochemistry.

[5]  W. MacNee,et al.  Aluminium lactate treatment of DQ12 quartz inhibits its ability to cause inflammation, chemokine expression, and nuclear factor-kappaB activation. , 2001, Toxicology and applied pharmacology.

[6]  G. Weissmann,et al.  Tumor necrosis factor provokes superoxide anion generation from neutrophils. , 1986, Biochemical and biophysical research communications.

[7]  L. Rossetti,et al.  An evaluation of chelex-based DNA purification protocols for the typing of lactic acid bacteria. , 2000, Journal of microbiological methods.

[8]  S. Bartnicki-García,et al.  Biosynthesis of β-1,3- and β-1,6-linked glucan by Phytophthoracinnamomi hyphal walls☆ , 1966 .

[9]  E. Bayer,et al.  Ligand-exchange chromatography of amino acids on copper-, cobalt- and zinc-chelex 100. , 1975, Journal of chromatography.

[10]  J. Antonini,et al.  Effect of welding fume solubility on lung macrophage viability and function in vitro. , 1999, Journal of toxicology and environmental health. Part A.

[11]  T. Eagar,et al.  Study of Chromium in Gas Metal Arc Welding Fume , 2004 .

[12]  J. Antonini,et al.  Freshly generated stainless steel welding fume induces greater lung inflammation in rats as compared to aged fume. , 1998, Toxicology letters.

[13]  W. MacNee,et al.  Role of transcription factors in inflammatory lung diseases , 1998, Thorax.

[14]  Kyu Hyuk Chung,et al.  Pattern of deposition of stainless steel welding fume particles inhaled into the respiratory systems of Sprague-Dawley rats exposed to a novel welding fume generating system. , 2000, Toxicology letters.

[15]  J. Carter,et al.  Copper-dependent inflammation and nuclear factor-kappaB activation by particulate air pollution. , 1998, American journal of respiratory cell and molecular biology.

[16]  C. Pollack,et al.  Heavy metal toxicity, part II: lead and metal fume fever. , 1998, The Journal of emergency medicine.

[17]  M. Caude,et al.  Ligand exchange chromatography of amino acids on copper(II) modified silica gel with ultraviolet spectrophotometric detection at 210 nanometers , 1979 .

[18]  M. Blagosklonny,et al.  Carcinogenic metals induce hypoxia-inducible factor-stimulated transcription by reactive oxygen species-independent mechanism. , 2000, Cancer research.

[19]  G. Oberdörster,et al.  Pulmonary retention of ultrafine and fine particles in rats. , 1992, American journal of respiratory cell and molecular biology.

[20]  D. Costa,et al.  Oxidant Generation and Lung Injury after Particulate Air Pollutant Exposure Increase with the Concentrations of Associated Metals , 1996 .

[21]  K. Oshita,et al.  Development of column-pretreatment chelating resins for matrix elimination/multi-element determination by inductively coupled plasma-mass spectrometry. , 2002, The Analyst.

[22]  W. MacNee,et al.  Activation of NF-κB by PM10 Occurs via an Iron-Mediated Mechanism in the Absence of IκB Degradation , 2000 .

[23]  D. Costa,et al.  In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. , 1997, Chemical research in toxicology.

[24]  J. Gordon.  Use of vanadate as protein-phosphotyrosine phosphatase inhibitor. , 1991, Methods in enzymology.

[25]  M. S. Bernstein,et al.  Cytokines in metal fume fever. , 1993, The American review of respiratory disease.

[26]  U. Kodavanti,et al.  PULMONARY PROINFLAMMATORY GENE INDUCTION FOLLOWING ACUTE EXPOSURE TO RESIDUAL OIL FLY ASH: ROLES OF PARTICLE-ASSOCIATED METALS , 1997 .

[27]  D. Costa,et al.  Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. , 1997, Environmental health perspectives.

[28]  I. Rahman,et al.  Inflammation and the regulation of glutathione level in lung epithelial cells. , 1999, Antioxidants & redox signaling.

[29]  W. MacNee,et al.  Oxidative stress and regulation of glutathione in lung inflammation. , 2000, The European respiratory journal.

[30]  W. MacNee,et al.  Transcriptional regulation of gamma-glutamylcysteine synthetase-heavy subunit by oxidants in human alveolar epithelial cells. , 1996, Biochemical and biophysical research communications.

[31]  Xianglin Shi,et al.  The role of oxygen free radicals in occupational and environmental lung diseases. , 1997, Environmental health perspectives.

[32]  K. Driscoll,et al.  Pulmonary response to inhaled silica or titanium dioxide. , 1991, Toxicology and applied pharmacology.

[33]  L. Bidstrup.  HEALTH of welders. , 1951, Lancet.

[34]  K. Adler,et al.  Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[35]  S. Weitzman,et al.  Asbestos-catalysed lipid peroxidation and its inhibition by desferroxamine. , 1985, The Biochemical journal.

[36]  B. Blount,et al.  Two types of metal fume fever: mild vs. serious. , 1990, Military medicine.

[37]  I. Adamson,et al.  Pulmonary toxicity of an atmospheric particulate sample is due to the soluble fraction. , 1999, Toxicology and applied pharmacology.

[38]  A. Ghio,et al.  EFFECT OF METAL REMOVAL ON THE TOXICITY OF AIRBORNE PARTICULATE MATTER FROM THE UTAH VALLEY , 2002, Inhalation toxicology.

[39]  W. MacNee,et al.  Short-term inflammatory responses following intratracheal instillation of fine and ultrafine carbon black in rats. , 1999, Inhalation toxicology.

[40]  D. Costa,et al.  Soluble transition metals mediate residual oil fly ash induced acute lung injury. , 1997, Journal of toxicology and environmental health.

[41]  B. Nemery,et al.  Metal toxicity and the respiratory tract. , 1990, The European respiratory journal.

[42]  D. Bagchi,et al.  Oxidative mechanisms in the toxicity of metal ions. , 1995, Free radical biology & medicine.

[43]  W. Beckett,et al.  The respiratory health of welders. , 1991, The American review of respiratory disease.

[44]  G. M. Ridder,et al.  Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology. , 1990, American journal of respiratory cell and molecular biology.

[45]  David M. Brown,et al.  Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. , 2001, Toxicology and applied pharmacology.

[46]  W. MacNee,et al.  Adverse health effects of PM10 particles: involvement of iron in generation of hydroxyl radical. , 1996, Occupational and environmental medicine.

[47]  M. Lag,et al.  Importance of soluble metals and reactive oxygen species for cytokine release induced by mineral particles. , 2001, Toxicology.

[48]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[49]  S. Toyokuni,et al.  Iron-induced carcinogenesis: the role of redox regulation. , 1996, Free radical biology & medicine.

[50]  J. Antonini,et al.  Pneumotoxicity and pulmonary clearance of different welding fumes after intratracheal instillation in the rat. , 1996, Toxicology and applied pharmacology.

[51]  J. Carter,et al.  Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. , 1997, Toxicology and applied pharmacology.

[52]  S. Mizel,et al.  Interleukin 1, a potential regulator of fibroblast proliferation. , 1982, Journal of immunology.

[53]  W. Kuschner,et al.  Early pulmonary cytokine responses to zinc oxide fume inhalation. , 1997, Environmental research.

[54]  I. Adamson,et al.  Zinc is the toxic factor in the lung response to an atmospheric particulate sample. , 2000, Toxicology and applied pharmacology.

[55]  H. Boushey,et al.  Pulmonary responses to purified zinc oxide fume. , 1995, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[56]  J. W. Winchester,et al.  Particle size distribution and human respiratory deposition of trace metals in indoor work environments. , 1976, The Annals of occupational hygiene.