Grantee Research Project Results

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: Center for the Study of Childhood Asthma in the Urban Environment
Center Director: Hansel, Nadia
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 , Human 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

Publications Views
Other subproject views:	All 7 publications	7 publications in selected types	All 7 journal articles
Other center views:	All 117 publications	116 publications in selected types	All 113 journal articles

Publications
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 Full-text: Proceedings of the American Thoracic Society-Full Text HTML Exit Abstract: Proceedings of the American Thoracic Society-Abstract Exit Other: Proceedings of the American Thoracic Society-Full Text PDF Exit
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)	Abstract from PubMed Full-text: ERJ-Full Text HTML Exit Abstract: ERJ-Abstract Exit Other: ERJ-Full Text PDF Exit
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)	Abstract from PubMed Abstract: Wiley-Abstract Exit
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)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Karger-Full Text PDF Exit Abstract: Karger-Abstract Exit

Supplemental Keywords:

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

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R832139 Center for the Study of 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

Top of Page

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.