Superfund Research Program
Environmentally Persistent Free Radicals Alter Pulmonary Immunologic Homeostasis
Project Leader: Stephania A. Cormier
Grant Number: P42ES013648
Funding Period: 2011-2018
- Project Summary
Project Summary (2011-2018)
Epidemiological data demonstrate associated increases in particulate matter (PM) with increases in acute asthma exacerbations and the risk of developing asthma; however, the reasons for these increases are poorly understood. Dr. Cormier's research group seeks 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 free 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. The researchers 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, researchers believe they play a major role in EPFR-associated lung disease. This led them 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, the researchers propose three aims:
- Define the immunological and pathophysiological impact of acute and chronic inhalation exposures to EPFRs in normal and diseased lungs;
- Determine the significance of pulmonary DCs in the pathophysiological response to EPFR exposure; and
- Illustrate the role of the Th17 lymphocyte subset in EPFR-induced asthma.
This work will significantly advance Dr. Cormier's 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.