Epidemiological data demonstrate associated increases in particulate matter (PM) with increases in acute asthma exacerbations and risk of developing asthma;however, the reasons for these increases are poorly understood. We seek to establish the mechanism by which exposure to PM from Superfund sites modulates pulmonary immune homeostasis and results in the development of asthma. Asthma affects 300 million people worldwide, and its prevalence has been steadily increasing. The presence of a newly realized class of pollutants, environmentally persistent radicals (EPFRs), in contaminated soils at Superfund sites and PM from combustion and thermal treatment of hazardous substances suggests a potentially unrecognized risk factor for the development and/or exacerbation of asthma. We demonstrate that acute inhalation exposures to EPFRs in rodents initiate inflammatory responses in the lung characterized by an influx of neutrophils, occlusion of alveolar spaces, and increased bronchial hyperreactivity;all of which are indicative of severe asthma in humans. This occurs concurrently with the influx of both CD4+ and CD8+ lymphocytes and of dendritic cells (DCs) into the lung. Since DCs orchestrate many pulmonary immune responses, we believe they play a major role in EPFR-associated lung disease. This led us to the overall hypothesis: particle associated EPFRs initiate immunological changes that predispose to asthma by altering dendritic cell (DC) function such that Th17 responses are favored. To test this, we propose three aims.
Aim 1 will define the immunological and pathophysiological impact of acute and chronic inhalation exposures to EPFRs in normal and diseased lungs.
Aim 2 will determine the significance of pulmonary DCs in the pathophysiological response to EPFR exposure.
Aim 3 will illustrate the role of the Thi 7 lymphocyte subset in EPFR-induced asthma. This work will significantly advance our understanding of DC responses to xenobiotics and DC-induced immunotoxicity. This project draws on the strong complementary skills, unique expertise and resources in LSU-SRP's tightly synergist group and depends heavily on the shared samples, knowledge, and technical proficiency provided by the Cores.

Public Health Relevance

Our studies will provide insight into how contaminated soils and PM produced from thermal treatment affects the development and progression of inflammatory airways disease (i.e. asthma) and provide a rational framework for clinical studies of antioxidant and cytokine modulation strategies to prevent EPFR-associated disease exacerbation. These studies will have important implications for public health and environmental policy, since there are currently no rules or regulations for limiting or monitoring EPFRs in the environment.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
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Louisiana State University A&M Col Baton Rouge
Baton Rouge
United States
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Hijano, Diego R; Siefker, David T; Shrestha, Bishwas et al. (2018) Type I Interferon Potentiates IgA Immunity to Respiratory Syncytial Virus Infection During Infancy. Sci Rep 8:11034
Haywood, Benjamin J; White, John R; Cook, Robert L (2018) Investigation of an early season river flood pulse: Carbon cycling in a subtropical estuary. Sci Total Environ 635:867-877
Connick, J Patrick; Reed, James R; Backes, Wayne L (2018) Characterization of Interactions Among CYP1A2, CYP2B4, and NADPH-cytochrome P450 Reductase: Identification of Specific Protein Complexes. Drug Metab Dispos 46:197-203
Potter, Phillip M; Guan, Xia; Lomnicki, Slawomir M (2018) Synergy of iron and copper oxides in the catalytic formation of PCDD/Fs from 2-monochlorophenol. Chemosphere 203:96-103
Harmon, Ashlyn C; Hebert, Valeria Y; Cormier, Stephania A et al. (2018) Particulate matter containing environmentally persistent free radicals induces AhR-dependent cytokine and reactive oxygen species production in human bronchial epithelial cells. PLoS One 13:e0205412
Jaligama, Sridhar; Patel, Vivek S; Wang, Pingli et al. (2018) Radical containing combustion derived particulate matter enhance pulmonary Th17 inflammation via the aryl hydrocarbon receptor. Part Fibre Toxicol 15:20
Dugas, Tammy R (2018) Unraveling mechanisms of toxicant-induced oxidative stress in cardiovascular disease. Curr Opin Toxicol 7:1-8
Oyana, Tonny J; Podila, Pradeep; Wesley, Jagila Minso et al. (2017) Spatiotemporal patterns of childhood asthma hospitalization and utilization in Memphis Metropolitan Area from 2005 to 2015. J Asthma 54:842-855
Deese, Rachel D; Weldeghiorghis, Thomas K; Haywood, Benjamin J et al. (2017) Influence of surfactants and humic acids on Artemia Franciscana's embryonic phospho-metabolite profile as measured by31P NMR. Aquat Toxicol 186:188-195
Reed, James R; Backes, Wayne L (2017) Physical Studies of P450-P450 Interactions: Predicting Quaternary Structures of P450 Complexes in Membranes from Their X-ray Crystal Structures. Front Pharmacol 8:28

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