Impact/Purpose:

These studies are designed to address specific mechanistic hypotheses regarding the interactions between inhaled ultrafine particles and specific pulmonary and cardiovascular cell populations. We will use cell lines and primary cells derived from rats and humans to test the hypothesis that increased morbidity and mortality in susceptible populations is due to the unique characteristics of ultrafine particles inducing oxidative stress and activation of target cells. It is further suggested that this ability is based on composition that is related to specific sources.

Description:

The results of these in vitro studies will identify specific mechanisms that are triggered following particle cell contact in a cell specific context and identify markers of cellular response. We predict that many of the subsequent physiologic effects in vivo are the consequences of cellular oxidative stress, cell activation and apoptosis. The proposed in vitro experiments will provide a link between the whole animal and controlled clinical (human) exposures, described in the other programs of this PM Center, By evaluating "source specific" responses in vitro we can determine the relative potency of a given particle type and allow for studies in vivo to be more focused and mechanism based. These studies may also provide information regarding strategies to reduce PM effects. As correlations are established between in vitro responses and whole organism studies, the in vitro studies, which require less material and a shorter time frame, may be applied as a routine screen for potential PM risk and as support for setting regulatory standards.

URLs/Downloads:

2009 Progress Report

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Record Details:

Record Type:PROJECT( ABSTRACT )

Start Date:10/01/2005

Completion Date:09/30/2010

Record ID: 144573

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Related Organizations:

Role :OWNER

Organization Name :UNIVERSITY OF CALIFORNIA - SAN DIEGO

Organization Name :RPCA



Role :OWNER

Organization Name :UNIVERSITY OF ROCHESTER

Organization Name :RPCA

Project Information:

Approach :

Studies will use isolated and cultured cells that have been identified as the principle targets of inhaled PM and carry out hypothesis testing studies that support the in vivo studies (Cores 3 and 4). Cell specific endpoints of PM induced toxicity for inflammatory, epithelial and vascular endothelial cells will be determined in a dose-responsive manner. These cells will be obtained from both human and animal tissues. Our use of multiple endpoints ensures that we can determine the relationship between a cellular response and the critical variable of a specific particle. We plan studies with both "real world" and laboratory generated PM of known composition that may represent specific sources to establish source related effects.

Cost :$.00

Research Component :Health Effects

Project IDs:

ID Code :R832415C005

Project type :Center