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MECHANISMS BY WHICH ULTRAFINE, FINE, AND COARSE PARTICLES CAUSE ADVERSE HEALTH EFFECTS
Impact/Purpose:
The goal of this project is to understand whether coarse, fine, or ultrafine particles exert effects via similar or different mechanisms and whether these differences are related to specific components present in each of the size ranges.
Description:
A small number of recent studies suggest that different size particles may cause different health effects. There are clearly differences in the chemical makeup of coarse, fine, and ultrafine particles, and this different chemistry may well drive different health responses. The role of biological compounds, (specifically LPS, which is primarily present in coarse PM) will be assessed by exposure of healthy volunteers and asthmatics to this agent. Cardiopulmonary changes will be assessed following exposure and specific cellular and physiological mechanisms that drive the response will be characterized. UF, F, C particles will be collected from Chapel Hill, and other locations as appropriate. Micro-array and other molecular approaches will be used to identify specific genes, gene families, and cellular pathways which are uniquely altered following exposure to each of the size fractions. In addition, the signal transduction pathways activated by each size class will be characterized. These studies have the potential to identify biomarkers of exposure, as well as characterize mechanisms by which each size class causes adverse health effects. To demonstrate in vivo relevance of these in vivo studies, selected samples will also be instilled into appropriate animal models and cardiopulmonary end points assessed. Use of animal and human cells will also provide information about species sensitivity that will be useful for purposes of extrapolation from animals to humans.