Grantee Research Project Results

Mechanisms of Particulate-Induced Mediator Expression in Human Airway Epithelial Cells

EPA Grant Number: R826270
Title: Mechanisms of Particulate-Induced Mediator Expression in Human Airway Epithelial Cells
Investigators:
Institution: University of North Carolina at Chapel Hill
EPA Project Officer: Chung, Serena
Project Period: December 15, 1997 through December 14, 2000
Project Amount: $374,170
RFA: Health Effects and Exposures to Particulate Matter and Associated Air Pollutants (1997) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air , Human Health

Description:

This project addresses possible biological mechanisms underlying the adverse human health effects associated with exposure to the respirable fine particulate matter present in air pollution (PM2.5). Epidemiological studies suggest that humans, especially those with chronic pulmonary or cardiovascular disease, are adversely affected by exposure to PM2.5 and animal toxicological studies have shown that PM2.5 introduced into the respiratory tract cause adverse health effects such as inflammation. In order to bridge the gap between human epidemiological and animal toxicological studies, this research will investigate the effects of PM2.5 upon human respiratory tract epithelial cells. The underlying hypothesis of this research is that respirable particulates carry as yet unidentified toxic environmental chemicals into the respiratory tract where they are deposited onto the epithelial cell lining and act to disrupt normal epithelial cell functions, resulting in inflammation.

Approach:

The proinflammatory response of human respiratory tract epithelial cells cultured in the laboratory and exposed to PM2.5 collected from the environment will be characterized. Emphasis will be placed upon understanding what biochemical processes within these cells are altered by PM2.5 exposure and how fine particulates disrupt these processes. The same particulates that have been used in many of the animal toxicological studies will be used in these studies, so that the results will be comparable between human and animal studies.

Expected Results:

Descriptive and mechanistic information about proinflammatory responses in human respiratory tract epithelial cells caused by exposure to PM2.5 will be directly valuable to the understanding of pathophysiological mechanisms underlying the association between PM2.5 exposure and the adverse human health effects observed in epidemiological studies. Such data will be useful in the validation of animal models of human respiratory toxicology, and will serve as a base to develop studies of the effects of repeated, intermittent PM2.5 exposure. The latter are especially relevant to possible irreversible effects and to chronic exposure studies in animals, and ultimately to decisions about the form as well as the level of the NAAQS for PM2.5.

Publications and Presentations:

Publications have been submitted on this project: View all 4 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 4 journal articles for this project

Supplemental Keywords:

ambient air, PM10, residual oil fly ash, metals, transition metals, oxidants, sulfates, health effects, immunotoxicology, cellular, biology, cell biology, molecular biology., RFA, Scientific Discipline, Health, Air, particulate matter, Toxicology, Environmental Chemistry, Health Risk Assessment, air toxics, Environmental Microbiology, Risk Assessments, Biochemistry, Molecular Biology/Genetics, particle induced mediator expression, PM10, airway epithelial cells, cardiopulmonary responses, human health effects, PM 2.5, exposure and effects, biological mechanisms, cardiopulmonary mechanisms, chronic health effects, pulmonary, human exposure, animal toxicological studies, immunotoxicology

Progress and Final Reports:

1998

1999

Final Report