Jonathan Shannahan, PhD, Principal Investigator

Li Xia, Research Trainee

Welding is an essential modern manufacturing technology, with 11 million welders worldwide and 110 million individuals exposed to welding fumes at their workplace. Importantly, there exists an occupational exposure risk to welding fume exposures with studies demonstrating exposure-related lung dysfunction, asthma, bronchitis, cancer, and increased susceptibility to pulmonary infections. Welding fumes are a complex mixture consisting of primarily metal NPs, such as iron (Fe), manganese (Mn), and others. These metal NPs are able to deposit deep within the lung inducing oxidative stress and inflammation resulting in pulmonary injury. Toxicity resulting from welding fume exposure is likely variable based on alterations in NP components of the fumes. Additionally, welders are known to be increasingly susceptible to pulmonary bacterial and viral infections due to exposure-induced immune dysregulation. This modulation of the immune system may also reduce viral vaccine effectiveness in this population. To examine toxicity associated with variations in NP components of welding fumes, we constructed a system for the controlled and continuous generation of NPs from welding electrodes for in vitro exposure studies. For the proposed study, NP mixtures will be produced from highly utilized commercially available electrodes (6010, 6012, 7024). To perform hazard assessments of the NP components, human lung epithelial cells and macrophages will be grown individually and transitioned to air-liquid-interface. Human fibroblasts will be grown in the basolateral compartment and will interact with signaling molecules released from cells in air-liquid-interface. NP aerosols will be characterized in real-time during exposures for size, composition, and morphology. Cells will be exposed to two human-relevant concentrations of freshly aerosolized NPs for 8 h and endpoints of toxicity will be evaluated. In aim 1, cells will be examined for differential toxicity due to alterations in aerosolized NP components. The endpoints analyzed include cytotoxicity, internalization of NPs, and alterations in markers of oxidative stress, inflammation, and fibrosis. Aim 2 will evaluate bacterial and viral susceptibility risks following welding fume exposures through challenging exposed cells with lipopolysaccharide (LPS) to model gram-negative bacteria or the live attenuated influenza virus (FluMist). Completion of this proposed research will result in the generation of new knowledge regarding hazards associated with the NP component of welding fumes and their impact on infection risk. This information will allow for a more thorough understanding of disease associated with occupational exposure to welding fumes and can be applied to regulations, prevention strategies, and therapeutic strategies.