Grantee Research Project Results

Mechanisms of Ozone Toxicity to the Lung

EPA Grant Number: R825702C014
Subproject: this is subproject number 014 , established and managed by the Center Director under grant R825702
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children
Center Director: Schwartz, David A.
Title: Mechanisms of Ozone Toxicity to the Lung
Investigators: White, Carl W. , Murphy, Robert C.
Institution: National Jewish Medical and Research Center
EPA Project Officer: Chung, Serena
Project Period: February 16, 1998 through February 28, 2003 (Extended to February 28, 2004)
RFA: Environmental Lung Disease Center (National Jewish Medical and Research Center) (1998) RFA Text | Recipients Lists
Research Category: Targeted Research

Objective:

The objectives of this research project are to: (1) determine the effect of ozone on mitochondrial function and energetics (ATP) in lung epithelial cells (A549 cell line and primary epithelial cells); (2) determine the structure of novel phospholipids produced during exposure of purified lipids, isolated plasma membranes, and intact cells to ozone; and (3) evaluate effects of novel phospholipids, proteins, and/or protein/lipid products on epithelial cell viability, respiration, and mitochondrial membrane potential.

Significance of Research
The concept that lipid oxidation or ozonation products could incite pulmonary inflammation and/or damage is not entirely new, however this research project is intended to provide support for existing concepts in this area. In addition, the researchers novel approach, where whole surfactant will be first reacted with ozone and then fractionated and tested for cytotoxic effects, is intended to lead to the identification of two major types of toxic lipid products: 9-al and cholesterol oxidation products.

In addition to the research goals listed above, it should be noted that ATP analogs also will be developed as therapeutic agents. Because changes in survival of airway epithelium may be mediated by ozone in susceptible individuals, ATP analogs could have different roles in treatment of individuals that reside in high pollution areas.

Importance to the U.S. Environmental Protection Agency
In addition to the considerations discussed in the sections above, it is the goal of this research to provide findings that may have implications for guidelines and restrictions upon ambient ozone levels, especially with respect to certain high-risk populations.

Publications and Presentations:

Publications have been submitted on this subproject: View all 3 publications for this subproject | View all 132 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 3 journal articles for this subproject | View all 110 journal articles for this center

Supplemental Keywords:

air toxics, acute lung injury, air pollutants, airway disease, animal studies, environmental toxicant, exposure, genetic susceptibility, health effects, human exposure, human health risk, lung disease, lung epithelial cells, occupational disease, occupational exposure;, RFA, Health, Economic, Social, & Behavioral Science Research Program, Scientific Discipline, Health Risk Assessment, Epidemiology, Risk Assessments, Disease & Cumulative Effects, Environmental Statistics, Biology, biostatistics, database management, biomarkers, lung disease, statistical models, data analysis, data models, data quality assurance, exposure assessment, statistical methods

Progress and Final Reports:

Main Center Abstract and Reports:

R825702 Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R825702C001 SP-A and SP-D in Environmental Lung Disease
R825702C003 Adaptation to Nitrogen Dioxide: Role of Altered Glycolytic Pathway Enzyme Expression and NF-κB-Dependent Cellular Defenses Against Apoptosis
R825702C005 Inhalation of Particulate Matter Alters the Allergic Airway Response to Inhaled Allergen
R825702C006 Particle-Induced Lung Inflammation and Extracellular EC-SOD
R825702C007 Indoor-Outdoor Relationships of Airborne Particle Count and Endotoxin Concentrations
R825702C008 The Role of Mitochondrial DNA Mutations in Oxidant-Mediated Lung Injury
R825702C009 Immunopathogenesis of Hypersensitivity Pneumonitis in the Mouse
R825702C010 Activation of Natural T Lymphocytes by Diesel Exhaust Particulates Leads to Their Production of Interleukin-4 and TH2 Lymphocyte Differentiation to Allergen
R825702C011 Latex Antigen Levels During Powdered and Powderless Glove Use
R825702C012 Adjuvant Effects of Ozone in a Model of Allergen-Induced Airway Inflammation and Hyperresponsiveness
R825702C013 Acute Exposure to Particulate Air Pollution in Childhood Asthma
R825702C014 Mechanisms of Ozone Toxicity to the Lung

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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.