Effects of Concentrated Ambient Particles and Diesel Emissions on Rat Airways

EPA Grant Number: R832347C145
Subproject: this is subproject number 145 , established and managed by the Center Director under grant R832347
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Effects of Concentrated Ambient Particles and Diesel Emissions on Rat Airways
Investigators: Harkema, Jack
Institution: Michigan State University , Health Effects Institute
EPA Project Officer: Hunt, Sherri
Project Period: April 1, 2005 through March 31, 2010
RFA: Health Effects Institute (2005) RFA Text |  Recipients Lists
Research Category: Health Effects , Air Quality and Air Toxics , Air

Objective:

In the 1990s, results from several epidemiologic and controlled-exposure studies suggested an association between exposure to air pollution from traffic-derived particulate matter (PM) and increases in symptoms of airway diseases, including exacerbation of asthma. Some results also suggested that exhaust from diesel engines contributed to these effects.  Dr. Jack R. Harkema, Michigan State University (MSU), and colleagues proposed a study to investigate how the inhalation of PM2.5 (PM with an aerodynamic diameter ≤ 2.5 μm) concentrated from ambient air (concentrated ambient particles, CAPs) or diesel engine exhaust (DEE) would affect the airway inflammatory and allergic responses to the airborne allergen ovalbumin (OVA) in a rat model of asthma.

The investigators propose undertaking research that will expose rats to the pollutants at critical points in the induction of the allergic response, namely, the initial or sensitization phase and the second or challenge phase. The investigators hypothesized that inhalation of CAPs or DEE during sensitization or challenge would enhance inflammatory responses in the airways. 

Approach:

The investigators will design and conduct a descriptive study to evaluate the effects of two pollutants — CAPs (concentrated PM2.5) and DEE — in a rodent model of asthma.  The study will be conducted in two different locations: the CAPs study in Michigan (exposures in Detroit and analysis at MSU in East Lansing) and the DEE study at the Lovelace Respiratory Research Institute (LRRI) in Albuquerque, New Mexico. The same OVA sensitization and challenge regimen will be used in both the CAPs and DEE studies: Brown Norway rats will be sensitized by intranasal instillation of a 0.5% solution of OVA (or saline, as a control) on days 1 through 3; they rested for days 4 through 14 and were challenged intra nasally with a 1.0% solution of OVA (or saline) on days 15 through 17.

In both the CAPs and DEE studies, rats will be killed on day 18 and airway tissues from the nose and lung Will be harvested and bronchoalveolar lavage fluid (BALF) will be collected. Total and differential cell counts and levels of secreted mucin glycoprotein (Muc5AC),total protein, elastase, β -glucuronidase, multiple cytokines, and other soluble mediators including OVA-specific immunoglobulin E (IgE) will be evaluated in the BALF. Fixed nasal, and proximal and distal axial pulmonary airways will be examined morphometrically to assess characteristics of inflammation in the airways, which included mucus cell metaplasia and an increase in stored intraepithelial mucosubstances (IM) in airway epithelial cells. The investigators also will use bromodeoxyuridine (BrdU) labeling to assess the number of surface epithelial cells synthesizing DNA in the axial airways. Levels of RNA specific for mucin and multiple cytokines will also be assessed in lung tissue.

Expected Results:

The investigators anticipate that they will successfully design and conduct  a descriptive study to evaluate the effects of two pollutants — CAPs (concentrated PM2.5) and DEE — in a rodent model of asthma.

Supplemental Keywords:

Health Effects, Air Quality, Air Toxics, ambient air, particulate matter, diesel emmisions, allergic response, asthma, concentrated ambient particles (CAPs), diesel engine exhaust (DEE)

Relevant Websites:

http://pubs.healtheffects.org/getfile.php?u=522 Exit

Main Center Abstract and Reports:

R832347    Health Effects Institute (2005 — 2010)

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832347C135 Mechanisms of Particulate Matter Toxicity in Neonatal and Young Adult Rat Lungs
R832347C136 Uptake and Inflammatory Effects of Nanoparticles in a Human Vascular Endothelial Cell Line
R832347C138 Health Effects of Real-World Exposure to Diesel Exhaust in Persons with Asthma
R832347C140 Extended Follow-Up and Spatial Analysis of the American Cancer Society Study Linking Particulate Air Pollution and Mortality
R832347C141 Air Pollution Effects on Ventricular Repolarization
R832347C143 Measurement and Modeling of Exposure to Selected Air Toxics for Health Effects Studies and Verification by Biomarkers
R832347C144 Genotoxicity of 1,3-Butadiene and Its Epoxy Intermediates
R832347C145 Effects of Concentrated Ambient Particles and Diesel Emissions on Rat Airways
R832347C147 Atmospheric Transformation of Diesel Emissions