2002 Progress Report: Health Effects of Ambient Air PM in Controlled Human ExposuresEPA Grant Number: R827351C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R827351
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: EPA NYU PM Center: Health Risks of PM Components
Center Director: N/A
Title: Health Effects of Ambient Air PM in Controlled Human Exposures
Investigators: Gordon, Terry , Chen, Lung Chi , Fine, Jeffery S , Reibman, Joan
Current Investigators: Gordon, Terry , Chen, Lung Chi , Reibman, Joan
Institution: New York University School of Medicine
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2002 through May 31, 2003
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
The general hypothesis of this research project is that concentrated ambient particulate matter (PM) will produce acute adverse respiratory and cardiovascular health outcomes in volunteers under controlled exposure conditions.
As a result of delays in obtaining Institutional Review Board approval and the development of a centrifugal concentrator for the human studies, little progress was made in the exposure of human subjects to concentrated ambient PM. Therefore, in consultation with Drs. Lippmann and Schlesinger, Drs. Reibman, Chen, and Gordon concentrated their efforts on the examination of the in vitro response of human bronchial epithelial cells to size-fractionated ambient PM. Based on the significant association between exposure to ambient PM and the exacerbation of allergic asthma, the potential for airway epithelial cells (primary culture) to modulate the immune system was examined.
Size-fractionated ambient PM was collected with a micro-orifice, uniform-deposit impactor (MOUDI) for 2-week intervals throughout the year and used to treat human bronchial epithelial cells obtained from normal human volunteers. We observed that the fraction of particles less than 0.18 µm produced a dose-dependent increase in granulocyte macrophage-colony stimulating factor (GM-CSF) released from the epithelial cells. GM-CSF is a cytokine that can elicit inflammation in the airways via an effect on eosinophils and also can modulate immune responses via effects on dendritic cells. There was no change in secreted GM-CSF in cells treated with larger-sized ambient particles or equivalent doses of carbon or Mount St. Helen dust particles, suggesting that the human epithelial cell response was not due to a general particle effect. Moreover, treatment of epithelial cells with endotoxins had no effect on GM-CSF. Further experiments with inhibitors demonstrated that mitogen-activated-protein-kinase (MAPK) pathways are involved in the ambient particle effects on GM-CSF secretion by epithelial cells. This research has resulted in two publications, and was used as preliminary data in a successful National Institute of Environmental Health Sciences (NIEHS) grant application by Dr. Reibman.
The followup in vitro study examined the upregulation of airway immune responses by particle-induced activation of human airway epithelial cells (Reibman, et al., 2003). Because the initiation and maintenance of airway immune responses in allergic diseases such as asthma are dependent on the specific activation of local airway dendritic cells (DCs), we hypothesized that alterations in the local cytokine microenvironment can influence the recruitment of specific subsets of immature DCs and their subsequent maturation. Importantly, in the airway, DCs reside in close proximity to airway epithelial cells (AEC). therefore, we examined the ability of primary culture human bronchial epithelial cells to synthesize and secrete the recently described CC-chemokine, MIP-3a/CCL20. Human airway epithelial cells were stimulated with pro-inflammatory cytokines tumor necrosis factor (TNF)-a and interleukin (IL)-1b or, because of their critical role in allergic diseases, IL-4 and IL-13. Cells also were exposed to small-size fractions of ambient PM. Each of these stimuli induced MIP-3a/CCL20 gene and protein expression. Moreover, these agents upregulated mitogen-activated protein kinase pathways in epithelial cells. These data suggest a mechanism by which PM-activated airway epithelial cells may facilitate recruitment of DC subsets to the airway.
No future activities are planned for this project.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
|Other subproject views:||All 3 publications||3 publications in selected types||All 3 journal articles|
|Other center views:||All 112 publications||101 publications in selected types||All 89 journal articles|
||Gordon T, Reibman J. Cardiovascular toxicity of inhaled ambient particulate matter. Toxicological Sciences 2000;56(1):2-4.||
||Reibman J, Hsu Y, Chen LC, Kumar A, Su WC, Choy W, Talbot A, Gordon T. Size fractions of ambient particulate matter induce granulocyte macrophage colony-stimulating factor in human bronchial epithelial cells by mitogen-activated protein kinase pathways. American Journal of Respiratory Cell and Molecular Biology 2002;27(4):455-462.||
||Reibman J, Hsu Y, Chen LC, Bleck B, Gordon T. Airway epithelial cells release MIP-3α/CCL20 in response to cytokines and ambient particulate matter. American Journal of Respiratory Cell and Molecular Biology 2003;28(6):648-654.||
Supplemental Keywords:air pollution, air pollutants, particulate matter, PM, fine particles, PM2.5, particulates, ambient PM, in vitro response, human bronchial epithelial cells, size-fractionated ambient PM, ambient PM exposure, allergic asthma, airway immune responses, allergic diseases, asthma, airway epithelial cells, immune system modulation, granulocyte macrophage-colony stimulating factor, GM-CSF, ambient particle effects, cytokine microenvironment, dendritic cells., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Environmental Monitoring, Physical Processes, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, air toxics, atmospheric particles, chemical characteristics, toxicology, ambient air monitoring, acute cardiovascular effects, airborne particulate matter, ozone, environmental risks, exposure, Sulfur dioxide, air pollution, aerosol composition, atmospheric aerosol particles, human exposure, PM, exposure assessment
Progress and Final Reports:Original Abstract
Main Center Abstract and Reports:R827351 EPA NYU PM Center: Health Risks of PM Components
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827351C001 Exposure Characterization Error
R827351C002 X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
R827351C003 Asthma Susceptibility to PM2.5
R827351C004 Health Effects of Ambient Air PM in Controlled Human Exposures
R827351C005 Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
R827351C006 Effects of Particle-Associated Irritants on the Cardiovascular System
R827351C007 Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
R827351C008 Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
R827351C009 Health Risks of Particulate Matter Components: Center Service Core
R827351C010 Lung Hypoxia as Potential Mechanisms for PM-Induced Health Effects
R827351C011 Urban PM2.5 Surface Chemistry and Interactions with Bronchoalveolar Lavage Fluid (BALF)
R827351C012 Subchronic PM2.5 Exposure Study at the NYU PM Center
R827351C013 Long Term Health Effects of Concentrated Ambient PM2.5
R827351C014 PM Components and NYC Respiratory and Cardiovascular Morbidity
R827351C015 Development of a Real-Time Monitoring System for Acidity and Soluble Components in Airborne Particulate Matter
R827351C016 Automated Real-Time Ambient Fine PM Monitoring System