Welding fume-induced generation of reactive oxygen species and activation of inflammatory signaling pathways in RAW 264.7 mouse macrophages

Details

• Personal Author:
  Antonini JM ; Bishop LM ; Erdely A ; Eye T ; Kodali V ; Meighan T ; Shoeb M
• Description:
  Welding fumes are a complex mixture of several toxic metals (e.g., Cr, Mn, Fe, Ni). Epidemiology indicates that welders have an increased risk for lung disease, including bronchitis, airway infections, and cancer. Animal toxicology studies show that specific welding fumes cause significant lung injury and inflammation, depending on the metal composition of the fume. The goal was to examine the potential mechanisms by which welding fumes with different metal compositions may generate reactive oxygen species (ROS) and activate inflammatory signaling pathways in an in vitro model. RAW 264.7 mouse macrophages were incubated with 0, 3.125, 6.25, 12.5, 25 and 50 microg/mL of either manual metal arc-stainless steel (MMA-SS) or gas metal arc-mild steel (GMA-MS) welding fumes for 24 hr. Cytotoxicity, ROS generation, and activation of different inflammatory markers were assessed. Metal composition and solubility of the fumes were different: MMA-SS (41% Fe, 29% Cr, 17% Mn) was highly water-soluble, whereas GMA-MS (85% Fe, 14% Mn) was water-insoluble. At 24 hr, MMA-SS significantly elevated ROS generation and dose-dependently increased cytotoxicity in the RAW 264.7 cells compared to GMA-MS and saline control. Welding fume-induced ROS generation led to production of the toxic lipid aldehyde, 4-hydroxynonenal (HNE). Both welding fumes induced the activation of the mitogen activated protein kinases (MAPK), such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), leading to the increased expression of COX-2 in the RAW 264.7 cells. Also, welding fumes increased protein expression of Nrf2 and HO-1, activating the Nrf2-Keap-HO-1pathway. In all cases, a significantly greater activation of the different inflammatory markers was observed for MMA-SS compared to the GMA-MS and saline control. These results suggest that the cytotoxicity of RAW 264.7 cells caused by MMA-SS is due to the presence of soluble and cytotoxic metals (Cr, Ni) that are absent in the GMA-MS fume. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Blood Chromium Cytotoxins Environmental Exposure Ferrous Compounds Immune System Inhalation Exposure Laboratories Lung Macrophages Manganese Metals Nickel Occupational Health Particulate Matter Respiratory System Safety Toxicology Welding

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• Keywords:
  Arc Welding Author Keywords: Particulates Cellular Effects Cellular Reactions Cytotoxicity Exposure Assessment Exposure Levels Fumes Immune Reaction Inflammation Inhalants Inhalation Toxicology Insoluble Compounds In Vitro Study Iron Laboratory Animals Laboratory Testing Lung Cells Lung Function Metal Compounds Metal Fumes Models Proteins Pulmonary Effects Pulmonary Function Reactive Oxygen Species ROS Soluble Stainless Steel Toxic Effects Welding Fume Welding Fumes

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  19
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047824
• Citation:
  Toxicologist 2016 Mar; 150(1)(Abstract Suppl):19
• CAS Registry Number:
  Chromium (CAS RN 7440-47-3) ; Iron (CAS RN 7439-89-6) ; Manganese (CAS RN 7439-96-5) ; Nickel (CAS RN 7440-02-0)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Supplement:
  Abstract Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a81aabe566b180ab285170cf1c6eeb2ec90d5369a07385f28fd350fb91c269b4d525e7be7a1a5733cbaec9bdc21776ca087b289026d7f124496689a577820d5a
• Download URL:
  https://stacks.cdc.gov/view/cdc/202792/cdc_202792_DS1.pdf
• File Type:
  [PDF - 4.99 MB ]