Grantee Research Project Results

Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro

EPA Grant Number: R827352C002
Subproject: this is subproject number 002 , 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 Children's Environmental Health Center
Center Director: McConnell, Rob Scot
Title: Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro
Investigators: Nel, Andre E.
Current Investigators: Nel, Andre E. , Cho, Arthur K. , Froines, John R. , Sioutas, Constantinos , Li, Ning
Institution: University of California - Los Angeles , University of Southern California , Michigan State University , University of California - Irvine
Current Institution: University of California - Los Angeles , University of Southern California
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Particulate Matter , Air Quality and Air Toxics , Air

Objective:

The overall objective of this research project is to focus on the central hypothesis of the Southern California Particle Center and Supersite, which is that organic constituents associated with particulate matter—including quinones, other organic compounds (polycyclic aromatic hydrocarbons [PAHs], nitro-PAHs, and aldehydes/ketones), and metals—are capable of generating reactive oxygen species (ROS) and acting as electrophilic agents. They have a central role in allergic airway disease such as asthma and cardiovascular effects through their ability to generate oxidative stress, inflammation, and immunomodulating effects in the lungs and airways.

The specific objectives of the research project are to: (1) establish a murine model for ovalbumin (OVA)-induced allergic inflammation and use that model for studying the adjuvant effects of the diesel exhaust particles (DEPs) on allergic inflammation; and (2) establish an in vitro model of toxicity in tissue culture macrophages and epithelial cells, in which the effects of particle composition can be studied in terms of oxidative stress effects, cytokine production, and induction of cytotoxicity (apoptosis).

We propose that the generation of oxidative stress in epithelial cells and macrophages leads to a hierarchical response, which is protective in nature, but may yield to injurious effects if the level of oxidative stress increases. We propose that the proinflammatory effects are responsible for the adjuvant effects of DEPs on allergic inflammation and asthma.

Publications and Presentations:

Publications have been submitted on this subproject: View all 15 publications for this subproject | View all 150 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 15 journal articles for this subproject | View all 149 journal articles for this center

Supplemental Keywords:

Particulate matter, quinones, PAHs, aldehydes, ketones, metals, allergic airway disease, human health risk, asthma, cardiovascular effects, oxidative stress, environmental monitoring, California, mobile sources, diesel exhaust particles, reactive oxygen species, in vitro modeling, antioxidant response element,, RFA, Health, Air, Scientific Discipline, Geographic Area, HUMAN HEALTH, Risk Assessments, State, particulate matter, Environmental Chemistry, Biochemistry, Health Effects, Air Pollutants, toxicity, diesel exhaust, California (CA), aerosols, diesel exhaust particulates, particle concentrator, ambient aerosol, asthma, human exposure, quinones, atmospheric chemistry, particulate exposure, particulates, allergens, toxicology, particle transport, air pollution, airborne urban contaminants, human health risk, PAH, human health effects, airway disease

Progress and Final Reports:

1999

2000

2001 Progress Report

2002 Progress Report

2003 Progress Report

2004

Final Report

Main Center Abstract and Reports:

R827352    Southern California Children's Environmental Health Center

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)