Final Report: Dendritic Cell Activation by Particulate Matter and Allergen

EPA Grant Number: R832139C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R832139
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Johns Hopkins Center for Childhood Asthma in the Urban Environment
Center Director: Breysse, Patrick N.
Title: Dendritic Cell Activation by Particulate Matter and Allergen
Investigators: Georas, Steven
Institution: The Johns Hopkins University
EPA Project Officer: Callan, Richard
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

Objective:

The long term goal of the Center for Childhood Asthma in the Urban Environment was to examine how exposures to environmental pollutants and allergens may relate to airway inflammation and respiratory morbidity in children with asthma living in the inner city of Baltimore, and to search for new ways to reduce asthma morbidity by reducing exposure to these agents.
 
Project 4 examined the effect of Baltimore ambient particulates on maturation of peripheral blood monocytes to dendritic cells.

Summary/Accomplishments (Outputs/Outcomes):

This project investigated how particulate matter (PM) impacted the function of dendritic cells. When we began these studies, very little was known about the ability of this key cell type to recognize ambient PM. Dendritic cells are key sentinel cells in the body, and express an array of pattern recognition receptors and other molecules that sense the presence of environmental danger. We conducted two general sets of experiments supported by this project. First, we used human peripheral blood monocytes differentiated into dendritic cells in vivo using standard tissue culture techniques. Cells were obtained from peripheral blood and incubated with ambient Baltimore PM for different time frames and at different concentrations. These studies revealed that ambient PM induced a previously unreported phenotype in dendritic cells, allowing them to be better activators of T lymphocytes. Notably, the responding T cells secreted greater amounts of Th2 than Th1 cytokines. Therefore, this suggested that ambient PM could be sensed as a danger signal that might foster pro-allergic, Th2-dependent immune responses.
 
The second series of experiments we conducted were aimed at identifying how ambient PM activated dendritic cells mechanistically. Given the strong link between PM and oxidative stress, we speculated that reactive oxygen intermediates may be an intermediary. We tested this hypothesis using mouse bone marrow-derived dendritic cells in vitro, and indeed found that PM induced oxidant generation and activated dendritic cells in an occident-dependent manner.


Journal Articles on this Report : 4 Displayed | Download in RIS Format

Other subproject views: All 7 publications 7 publications in selected types All 7 journal articles
Other center views: All 113 publications 113 publications in selected types All 110 journal articles
Type Citation Sub Project Document Sources
Journal Article Georas SN. Inhaled glucocorticoids, lymphocytes, and dendritic cells in asthma and obstructive lung diseases. Proceedings of the American Thoracic Society 2004;1(3):215-221. R832139 (Final)
R832139C004 (Final)
  • Abstract from PubMed
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  • Abstract: Proceedings of the American Thoracic Society-Abstract
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  • Other: Proceedings of the American Thoracic Society-Full Text PDF
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  • Journal Article Georas SN, Guo J, De Fanis U, Casolaro V. T-helper type 2 regulation in allergic disease. European Respiratory Journal 2005;26(6):1119-1137. R832139 (2006)
    R832139 (Final)
    R832139C004 (Final)
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  • Full-text: ERJ-Full Text HTML
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  • Journal Article Georas SN, Berdyshev E, Hubbard W, Gorshkova IA, Usatyuk PV, Saatian B, Myers AC, Williams MA, Xiao HQ, Liu M, Natarajan V. Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental allergen challenge. Clinical and Experimental Allergy 2007;37(3):311-322. R832139 (2007)
    R832139 (Final)
    R832139C004 (Final)
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  • Journal Article Williams MA, Bauer S, Lu W, Guo J, Walter S, Bushnell TP, Lillehoj EP, Georas SN. Deletion of the mucin-like molecule muc1 enhances dendritic cell activation in response to toll-like receptor ligands. Journal of Innate Immunity 2010;2(2):123-143. R832139 (Final)
    R832139C004 (Final)
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, HUMAN HEALTH, particulate matter, Health Risk Assessment, Genetics, Allergens/Asthma, Health Effects, Physical Processes, asthma, children's health, asthma triggers, air toxics, exposure, air pollution, children, bioaerosols, air pollutant, human exposure, airborne pollutants, PM, allergens

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006 Progress Report
  • 2007 Progress Report
  • 2008
  • 2009

  • Main Center Abstract and Reports:

    R832139    Johns Hopkins Center for Childhood Asthma in the Urban Environment

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832139C001 The Epidemiology of Susceptibility to Airborne Particulates and Allergens to Asthma in African Americans
    R832139C002 A Randomized Controlled Trial of Behavior Changes in Home Exposure Control
    R832139C003 Mechanisms of Particulate-Induced Allergic Asthma
    R832139C004 Dendritic Cell Activation by Particulate Matter and Allergen