Grantee Research Project Results

Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains

EPA Grant Number: R827355C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R827355
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management
Center Director: Olabode, Lola
Title: Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains
Investigators: Luchtel, Daniel L. , Larson, Timothy V. , Lewtas, Joellen , Ladiges, Warren
Current Investigators: Luchtel, Daniel L. , Kavanagh, Terrance J , Baker, Coralie , Ceballos, Diana , McConnachie, Lisa , Rosenfeld, Michael , Leaman, Susan
Institution: University of Washington
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 30, 2004 (Extended to May 31, 2006)
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The toxicology project uses transgenic mouse strains, initially those selected for cardiovascular disease, as animal model(s) for exploring the mechanisms of PM-related acute morbidity and mortality. This model will be used to test the hypotheses that in compromised individuals (age, disease status), inhaled PM initiate production by cells in the lung of inflammatory mediators and oxidants, that then become blood-borne and target the cardiovascular system, leading to acute morbidity and mortality. Apart from use in validating and mechanistic studies, a susceptible mouse model will be useful in assessing relative potency of different ambient PM mixtures, leading to new hypotheses regarding causative agents. We hypothesize that inhaled PM causes release of inflammatory mediators from cells in the lung that become blood-borne and target the cardiovascular system, particularly the heart. In compromised individuals (age, diet, disease status), the cascade of mediators released from the lung acts on the cardiovascular system and causes acute morbidity and mortality. We will use transgenic mouse strains with specific cardiovascular genetic alterations to address the research need to identify potential health conditions that enhance susceptibility to adverse PM health effects. The nature of such health conditions should then provide insight into the biological mechanisms by which PM mediates acute and chronic health effects.

Publications and Presentations:

Publications have been submitted on this subproject: View all 8 publications for this subproject | View all 209 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 1 journal articles for this subproject | View all 109 journal articles for this center

Supplemental Keywords:

particulate matter, PM, human health effects, asthma, COPD, heart disease, Seattle, Spokane, Washington, WA, exposure, air pollution., Health, Scientific Discipline, Air, particulate matter, Toxicology, air toxics, Health Risk Assessment, Environmental Chemistry, Epidemiology, Risk Assessments, Biochemistry, Atmospheric Sciences, health effects, ambient aerosol, particulates, ambient air quality, air pollutants, morbidity, cardiopulmonary responses, human health effects, exposure and effects, animal model, hazardous air pollutants, exposure, air pollution, particle exposure, human exposure, atmospheric aerosols, ambient particle health effects, mortality studies, inhalation, mortality, particle transport, cardiovascular disease, human health risk, aerosols, atmospheric chemistry

Progress and Final Reports:

Main Center Abstract and Reports:

R827355 Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827355C001 Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality
R827355C002 Health Effects
R827355C003 Personal PM Exposure Assessment
R827355C004 Characterization of Fine Particulate Matter
R827355C005 Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains
R827355C006 Toxicology Project -- Controlled Exposure Facility
R827355C007 Health Effects Research Core
R827355C008 Exposure Core
R827355C009 Statistics and Data Core
R827355C010 Biomarker Core
R827355C011 Oxidation Stress Makers

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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.