Effects of Dung and Biomass Emissions on Macrophage Defenses, Gene Regulation, and Cellular Metabolism
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Effects of Dung and Biomass Emissions on Macrophage Defenses, Gene Regulation, and Cellular Metabolism

Abstract

Introduction: Human exposure to biomass smoke particulate matter has been documented to induce immunomodulatory effects that can promote respiratory and cardiovascular injuries. Despite the prevalent use of solid fuels and the potential detrimental impact on global health, the effects of specific solid biomass fuels on innate immune cell function remains poorly understood. Therefore, I aimed to begin to fill this gap by studying the effects of acute exposure to particulate matter emissions from dung and mixtures of dung with brushwood used with chulha and angithi traditional cookstoves commonly used in India, collected from in-field sampling. Methods: Particles collected on to Teflon filters in-field were extracted into aqueous suspension for cell-free and cellular in vitro toxicity assessment. The intrinsic cell-free oxidative capacity of particulate matter samples was compared to urban particulate matter and a single diesel quinone compound using dithiothreitol measures. Biological toxicity was assessed using submerged culture exposure with the macrophage-like RAW 264.7 cell line. Biological dose response changes in viability and innate immune function were assessed following four-hour exposures. Biochemical approaches were used to evaluate respiratory burst, metabolic activity, cell cycling dynamics, and gene expression changes. Associations between combustion emission factors, particle oxidative potential, and biological effects were evaluated using multivariate analysis to explore how particle toxicity is influenced by combustion processes. Results: PM emissions from dung-angithi combustion had higher oxidative potential measures than emissions from solid fuel use with chulha cookstoves. The oxidative potential of emissions from dung-chulha cookstoves were lower compared to all other sources of PM including urban dust and quinone compounds. Acute four-hour exposure to solid biomass particles altered critical innate immune respiratory burst function but did not reduce cell viability. Gene expression changes were observed following acute exposures in macrophages exposed to all the air pollutants studied here, including the downregulation of antioxidant response element transcription factor Nrf2 and antioxidant Gpx1, yet an upregulation of detoxifying enzyme Nqo1. However, differential gene expression patterns were observed for antioxidant Gsr, and metabolic housekeeping gene G6pd. The degree of particle reduction-oxidation (redox) activity, and biological respiratory burst dynamics and gene expression changes were associated with pyrolysis combustion processes that influence the generation of volatile organic compounds. Conclusions: In summary, this dissertation describes differences in the toxicity of air pollution particles from distinct sources. Particles generated by the combustion dung fuel and dung brushwood mixtures combustion commonly used with chulha and angithi cookstoves, induce innate immune cell changes through distinct mechanisms compared to urban dust and quinone. This study provides valuable insight into flaming, smoldering, and pyrolysis combustion processes that contribute to air pollution compositional differences and particle toxicity related to household cooking with solid biomass fuels.

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