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Final Report: Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
EPA Grant Number: R827352C004Subproject: this is subproject number 004 , established and managed by the Center Director under grant R827352
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Southern California Particle Center and Supersite
Center Director: Froines, John R.
Title: Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
Investigators: Kleinman, Michael T. , Cho, Arthur K. , Froines, John R. , Sioutas, Constantinos
Institution: University of California - Irvine , University of California - Los Angeles , University of Southern California
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter
Description:
Objective:Topic A: Studies Emphasizing Investigation of the Biological Mechanisms of Particulate Matter (PM) Effects in Relation to PM Physical and Chemical Characteristics
The objective of this study was to examine the effects of exposure to concentrated ambient particles (CAPs) from a heavily trafficked freeway on biomarkers of allergic and inflammatory responses in an asthma mouse model. A secondary objective was to examine pro-inflammatory biomarkers in brain tissue as a preliminary approach to the hypothesis that exposure to particulate matter could play a role in the onset or progression of neurodegenerative disorders, some of which can display an increase in oxidative and inflammatory events. Development of the particle concentrators and animal work were supported by funding from the California Air Resources Board as part of a five year program to develop and apply PM concentrators in health studies. The Southern California Particle Center and Supersite (SCPCS) supported concentrator operations, physicochemical characterization of the CAPs to which animals were exposed, and the examination of pro-inflammatory markers in brain tissue.
Summary/Accomplishments (Outputs/Outcomes):The goal of this study was to test the following hypotheses: (1) exposure to mobile emissions from mobile sources close to a heavily trafficked roadway will exacerbate airway inflammation and allergic airway responses in a sensitized mouse model, and (2) the magnitude of allergic airway disease responses will decrease with increasing distance from the roadway. An ambient particle concentrator was used to expose ovalbumin (OVA)-treated BALB/c mice to purified air and to fine (F) and ultrafine (UF) airborne particles at two distances, 50 m and 150 m, downwind of a roadway that is impacted by emissions from both heavy-duty diesel and light duty gasoline vehicles. Tissues and biological fluids from the mice were analyzed after exposures for 5 days per week in 2 consecutive weeks. The biomarkers of allergic or inflammatory responses that were assessed included cytokines released by Type 2 T-helper cells (IL-5, and IL-13), OVA-specific immunoglobulin E, OVA-specific immunoglobulin G1, and pulmonary infiltration of polymorphonuclear leukocytes and eosinophils. Allergy-related responses were increased in mice exposed to CAPs 50 m downwind of the road, compared to responses in mice exposed to purified air. No significant increases in allergy-related responses were observed in mice exposed to CAPs 150 m downwind of the road. The biological responses at the 50 m site were significantly associated with organic and elemental carbon components of F and UF suggesting that PM from motor vehicle fuel combustion could exert adjuvant effects and promote the development of allergic airway diseases.
We demonstrated that CAPs exposure increased inflammatory indices in brains of ovalbumin-sensitized BALB/c mice. Animals were divided into three exposure groups: filtered air (control), UF, or F and UF. The levels of proinflammatory cytokines interleukin-1 alpha (IL-1α) and tumor necrosis factor alpha (TNF-α) in the cytoplasm of brain tissue preparations were measured by immunoassay, and found to be increased in samples from mice exposed to particulate matter compared to that of control animals. Levels of the transcription factor NF-κB, which plays an important role in the expression of many immune system and pro-inflammatory compounds were also found to be substantially elevated in the brains of exposed mice compared with those of mice in the control group, as measured by an electrophoretic mobility shift assay. These findings suggest that components of inhaled particulate matter may trigger a proinflammatory response in nervous tissue that could contribute to the pathophysiology of neurodegenerative diseases. This small scale study is notable in that it identifies an important potential target tissue for the toxicity of particulate matter that has received little attention to date. If present in humans, brain inflammatory responses to particulate matter exposure could have a significant public health impact.
A full report to the California Air Resources Board (CARB) on this study is available for public download at: http://www.arb.ca.gov/research/abstracts/98-316a.htm 
, HUMAN HEALTH, Air, Geographic Area, Scientific Discipline, Health, RFA, Health Effects, Risk Assessments, Air Pollutants, Biochemistry, particulate matter, Environmental Chemistry, State, aerosols, California (CA), airborne urban contaminants, toxicity, allergens, particle concentrator, diesel exhaust particulates, diesel exhaust, human health risk, human health effects, particulates, toxicology, air pollution, airway disease, atmospheric chemistry, PAH, allergic airway disease, ambient aerosol, asthma, human exposure, animal model, particle transport, particulate exposure
Relevant Websites:
Progress and Final Reports:
2002 Progress Report
Original Abstract
Main Center Abstract and Reports:
R827352 Southern California Particle Center and Supersite
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827352C001 The Chemical Toxicology of Particulate Matter
R827352C002 Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro
R827352C003 Measurement of the “Effective” Surface Area of Ultrafine and Accumulation Mode PM (Pilot Project)
R827352C004 Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
R827352C005 Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)
R827352C006 Relationship Between Ultrafine Particle Size Distribution and Distance From Highways
R827352C007 Exposure to Vehicular Pollutants and Respiratory Health
R827352C008 Traffic Density and Human Reproductive Health
R827352C009 The Role of Quinones, Aldehydes, Polycyclic Aromatic Hydrocarbons, and other Atmospheric Transformation Products on Chronic Health Effects in Children
R827352C010 Novel Method for Measurement of Acrolein in Aerosols
R827352C011 Off-Line Sampling of Exhaled Nitric Oxide in Respiratory Health Surveys
R827352C012 Controlled Human Exposure Studies with Concentrated PM
R827352C013 Particle Size Distributions of Polycyclic Aromatic Hydrocarbons in the LAB
R827352C014 Physical and Chemical Characteristics of PM in the LAB (Source Receptor Study)
R827352C015 Exposure Assessment and Airshed Modeling Applications in Support of SCPC and CHS Projects
R827352C016 Particle Dosimetry
R827352C017 Conduct Research and Monitoring That Contributes to a Better Understanding of the Measurement, Sources, Size Distribution, Chemical Composition, Physical State, Spatial and Temporal Variability, and Health Effects of Suspended PM in the Los Angeles Basin (LAB)