ABOUT SCPC

Approach: We have assembled a team of highly respected researchers committed to developing a strong multidisciplinary program to address the challenging public health issues posed by PM pollution, with a focus on the unique urban setting of the Los Angeles air basin. Our research projects are united by a hypothesis that chemical composition and physical characteristics related to PM sources determine the toxicity and exposure-response of PM. Variations in exposure according to source, season, and location influence the resulting human health responses. The principal mechanistic hypothesis of the SCPC is that many health effects associated with PM exposure including adverse respiratory and cardiovascular outcomes derive from the induction of oxidative stress by reactive chemical species (organic or inorganic) in PM. Oxidative stress and inflammatory responses related to asthma and atherosclerosis are a particular focus. Integral to our toxicological hypothesis is the role of antioxidant defense pathways that protect against the pro-inflammatory effects of PM.

State-of-the-art portable particle concentrator technologies, deployed and refined over the previous five years of the SCPC, will be used for concentration and collection of ambient PM at sites selected to reflect the influence of major PM sources. Particle size distribution, chemical composition and airborne concentrations of resulting samples will be analyzed and coupled with source apportionment studies using chemical mass balance methods. Collected particles will be characterized in an extensive array of in vitro toxicology studies including chemical reactivity studies to investigate redox potential and early biological responses associated with the chemical constituents of PM. Our concentrators will be used to carry out dose-response studies of ambient PM toxicity in normal, sensitized and genetically susceptible animal models of asthma and atherosclerosis, to rigorously investigate biological mechanisms of PM-induced airway and vascular inflammation and disease exacerbation. In a susceptible human population (elderly persons with coronary heart disease), we will examine circulating biomarkers of exposure, oxidative stress, systemic inflammatory responses, and cardiovascular parameters to investigate the hypothesis that oxidative stress is a factor in cardiovascular outcomes associated with PM exposure. Potential modifying factors including genetic polymorphisms will be examined. Data from all projects will be pooled for evaluation of interrelationships between particle data, chemical and toxicological endpoints, and human biomarkers. Joint analysis will produce conclusions from the Center’s research that reach beyond the findings of individual projects.

Expected Benefits: The research proposed by the SCPC will provide extensive characterization of chemical composition, activity, and toxicological potential of a wide variety of ambient PM, including samples collected at freeways, air and sea ports, indoors and outdoors under varying climatological conditions. Results from the toxicological studies will provide a basis for identifying the important chemical and physical characteristics of PM sources that raise the greatest concern for public health in terms of the potential to induce oxidative stress and related health effects. Our work will examine specific mechanisms involved in induction and exacerbation of asthma and atherosclerosis, leading to a greater understanding of causal pathways along the continuum from particulate source through exposure to response. From a policy perspective the exposure-response relationships that emerge from the toxicological and human studies in relation to a variety of sources may be especially relevant. Our panel study of CHD patients and the work with genetically altered murine models will generate insights on the factors controlling susceptibility to PM-induced adverse effects that will prove useful in interpretation of other studies, protection of public health, and the design of future research. The human study provides information on particle sources and characteristics that affect intermediate endpoints in the progression of atherosclerosis and in acute changes in CV function and thrombosis. We also anticipate the development of new biomarkers for use in future studies. Overall, knowledge of the relative reactivity and resulting toxicity of atmospherically processed PM from key sources, and identification of exposure levels associated with specific toxic endpoints and health effects will provide critical input to the development of effective emission reduction strategies, especially in targeting those strategies to result in the greatest benefit to public health.