Compositional variations in metal nanoparticle components of welding fumes impact lung epithelial cell toxicity

J Toxicol Environ Health A. 2023 Oct 18;86(20):735-757. doi: 10.1080/15287394.2023.2238209. Epub 2023 Jul 24.

Abstract

Welding fumes contain harmful metals and gas by-products associated with development of lung dysfunction, asthma, bronchitis, and lung cancer. Two prominent welding fume particulate metal components are nanosized iron (Fe) and manganese (Mn) which might induce oxidative stress and inflammation resulting in pulmonary injury. Welding fume toxicity may be dependent upon metal nanoparticle (NP) components. To examine toxicity of welding fume NP components, a system was constructed for controlled and continuous NP generation from commercial welding and customized electrodes with varying proportions of Fe and Mn. Aerosols generated consisted of nanosized particles and were compositionally consistent with each electrode. Human alveolar lung A459 epithelial cells were exposed to freshly generated metal NP mixtures at a target concentration of 100 µg/m3 for 6 hr and then harvested for assessment of cytotoxicity, generation of reactive oxygen species (ROS), and alterations in the expression of genes and proteins involved in metal regulation, inflammatory responses, and oxidative stress. Aerosol exposures decreased cell viability and induced increased ROS production. Assessment of gene expression demonstrated variable up-regulation in cellular mechanisms related to metal transport and storage, inflammation, and oxidative stress based upon aerosol composition. Specifically, interleukin-8 (IL-8) demonstrated the most robust changes in both transcriptional and protein levels after exposure. Interleukin-8 has been determined to serve as a primary cytokine mediating inflammatory responses induced by welding fume exposures in alveolar epithelial cells. Overall, this study demonstrated variations in cellular responses to metal NP mixtures suggesting compositional variations in NP content within welding fumes may influence inhalation toxicity.

Keywords: Welding fumes; air-liquid interface exposure; composition; inflammation; metal oxide; metal storage; metal transport; nanoparticles mixtures; oxidative stress.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • A549 Cells
  • Cation Transport Proteins / genetics
  • Chemokines / analysis
  • Cytokines / analysis
  • Electrodes
  • Humans
  • Inflammation / chemically induced
  • Iron* / toxicity
  • Lung* / pathology
  • Manganese* / toxicity
  • Metal Nanoparticles* / toxicity
  • Occupational Exposure*
  • Reactive Oxygen Species / analysis
  • Transferrin / analysis
  • Welding*

Substances

  • Iron
  • Manganese
  • Reactive Oxygen Species
  • Cation Transport Proteins
  • Cytokines
  • Chemokines
  • Transferrin