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

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
• nanoparticles mixtures
• metal oxide
• composition
• air-liquid interface exposure
• metal transport
• metal storage
• inflammation
• oxidative stress

Acknowledgments

The authors would like to acknowledge the support from Dr. Keith Stantz and Yiu-Hsin Chang for training and guidance related to the use of Olympus B×41microscope to visualize and quantify transferrin. Additionally, this publication was supported by the Grant or Cooperative Agreement Number, T42 OH008455, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Data is available on request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15287394.2023.2238209

Additional information

Funding

This work was funded by the NIOSH Pilot Project Research Training Program, Grant T42 OH008455, Centers for Disease Control and Prevention.