Mechanisms of Toxicity of Particulate Matter (PM) Using Transgenic Mouse Strains.

The proposed toxicology project uses existing 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 initiates production by cells in the lung of inflammatory mediators and oxidants, that then become bloodborne 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 bloodborne 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.

Personnel

• Dan Luchtel,PhD. UW Department of Environmental Health
• Terry Kavanagh, PhD. UW Department of Environmental Health

Staff

• Research Scientist: Coralie Baker