Chemical composition and size of anthropogenic particulate matter affect biological responses in a rodent model
Citation:
Klein, L., Yong Ho Kim, Joseph Pancras, A. Johnstone, W. Williams, M. Schladweiler, W. Oshiro, Matthew Gilmour, AND S. Gavett. Chemical composition and size of anthropogenic particulate matter affect biological responses in a rodent model. 2024 Society of Toxicology, Salt Lake City, UT, March 10 - 14, 2024.
Impact/Purpose:
Previous studies of particulate matter toxicity examined how particle chemistry and size influence lung inflammation, injury, and pulmonary function, but no past study has fully evaluated each of these components in a comprehensive assessment of multiple types of PM. This study showed that exposure of mice to four different anthropogenic PM samples resulted in varied lung toxicity and functional responses that are likely attributable to differences in particle size and chemistry. Better understanding of the associations between PM composition and health effects may aid efforts to mitigate the impacts of PM exposure.
Description:
Background and Purpose: Particulate matter (PM) air pollution poses significant health risks within and beyond the respiratory system, but the physicochemical characteristics of anthropogenic PM that contribute to toxicity are not well understood. The purpose of this study was to examine the role of PM composition in the acute pulmonary responses to equal mass doses of urban ambient PM and fuel combustion PM in mice. Ambient PM included samples from Cleveland’s G.T. Craig monitoring site near an urban steel plant (GPM) and Ottawa’s urban airshed (OPM), while the fuel combustion PM included samples of residual oil fly ash (ROP) and diesel exhaust (DEP). Past studies have used different models to show that exposure to individual PM may promote lung inflammation, injury, and pulmonary function changes; however, no past study has fully evaluated each of these components in an integrated fashion. Here, we explore the influence of PM chemistry and size on biological responses including pro-inflammatory cytokines, pulmonary injury markers, and respiratory parameters concurrently in all four PM samples. Methods: The PM samples had distinct chemical compositions and sizes: GPM (high Fe, Al, Si, Ca, and Na) and OPM (high Pb and Zn) contained coarse particles (2.5-10 µm diameter), while ROP (high V, Ni, and Mg) and DEP (high polycyclic aromatic hydrocarbon (PAH) levels) contained fine particles (< 2.5 µm diameter). Female CD-1 mice were exposed to 100 µg of one PM in sterile saline or a saline vehicle alone via oropharyngeal aspiration and necropsied at 4 or 24 hr post-exposure. One hr prior to necropsy, mice were assessed for respiratory effects using whole body plethysmography, and data were compared with pre-exposure baseline values and the saline control group. At necropsy, bronchoalveolar lavage (BAL) fluid was collected for analysis of lung cellularity, cytokines, and markers of injury. Results: BAL neutrophil counts increased significantly in all exposure groups compared to the control, from 40- (DEP) to 80- (OPM) fold at 24 hr post-exposure. OPM and ROP significantly increased BAL protein, albumin, and lactate dehydrogenase levels at 24 hr post-exposure. At 4 hr post-exposure, IL-6 levels were significantly elevated in the GPM and OPM groups, and at 24 hr, levels were significantly elevated in the OPM and ROP groups. The GPM and OPM groups had significantly increased levels of TNF-α at 4 and 24 hr post-exposure. MIP-2 levels increased significantly in the GPM and OPM groups at 4 hr, but only the OPM increase remained significant at 24 hr. Only DEP exposure increased enhanced pause (Penh), an indicator of airflow limitation, at 24 hr post-exposure. GPM, OPM, and ROP samples produced many directional similarities in biological responses, and they shared significant levels of several metals, including Al, Fe, Pb, Mg, Ni, V, and Zn. Exposure to OPM, which had the highest levels of Pb and Zn, induced greater responses overall. DEP’s high PAH content may limit lung inflammation and injury compared to PM with high metal content, while still impeding lung function by restricting airflow. Conclusion: Exposure to anthropogenic PM samples resulted in varied lung toxicity and functional responses that may be attributable to differences in particle size and chemistry. Better understanding of the associations between PM composition and health effects may aid efforts to mitigate the impacts of PM exposure.