Project 4 -- Transport and Fate Particles

EPA Grant Number: R832414C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R832414
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Center Director: Wexler, Anthony S.
Title: Project 4 -- Transport and Fate Particles
Investigators: Wilson, Dennis , Louie, Angelique
Institution: University of California - Davis
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

1) To characterize the time course, tissue distribution, and mechanisms of particulate matter (PM) accumulation in the systemic circulation and target organs. 2) To evaluate the effects of size and surface-fixed charge on this process. 3) To determine how altered lung structure affects systemic particle distribution.

Approach:

Ultrafine particulates are transported into the systemic circulation and target organs by mechanisms that have not been characterized. Key questions include whether particulates in the ultrafine range behave differently from larger particles and whether particle composition, especially surface charge, affects systemic absorption. Experiments in this project will address the mechanisms of transport across the pulmonary epithelial barrier, the time course and target tissues for the distribution of particulates, likely means of intravascular transport, mechanisms of particulate interaction with the vascular wall, and the potential for endothelial cell mediated transport into tissues. We will perform in vivo exposures to particles of varied size and surface-fixed charge. These particulates will be composed of materials traceable by microimaging techniques in real time combined; particles will also be histologically quantitated within target tissues. We also propose in vitro experiments to evaluate potential routes of passive or facilitated transport across epithelial and endothelial cell monolayers. Finally we will determine whether animals with lung structure compromised by postnatal oxidant air pollutant exposure have increased systemic circulation of ultrafine particulates and examine the effect of acute oxidant exposure in adult animals on the transport of particles into the systemic circulation.

Expected Results:

These experiments use size and surface-fixed charge defined ultrafine particulates to provide baseline information on the time course and extent of their systemic absorption. Understanding the nature of particle transport in blood will be important for recognizing the likelihood and potential mechanisms for interaction with tissues. Combining microimaging of whole animals in real time with quantitative histologic evaluation of tissue distribution should provide insight into the time course and nature of potential biological responses. The high resolution microscopy and reconstruction techniques to be used in these experiments will not only distinguish whether particles move between or through cells and airway or vessels walls but, in combination with inhibitor studies, whether this is an active or passive process, thereby providing insight into the responsible biologic processes.

Publications and Presentations:

Publications have been submitted on this subproject: View all 3 publications for this subprojectView all 111 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 2 journal articles for this subprojectView all 48 journal articles for this center

Supplemental Keywords:

ambient air, ozone, exposure, health effects, human health, metabolism, sensitive populations, infants, children, PAH, metals, oxidants, agriculture, transportation,, RFA, Health, Air, particulate matter, Risk Assessments, toxicology, long term exposure, lung disease, epidemiological studies, PM

Progress and Final Reports:

2006 Progress Report
2007 Progress Report
2008 Progress Report
2009 Progress Report
2010 Progress Report
Final Report


Main Center Abstract and Reports:

R832414    San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832414C001 Project 1 -- Pulmonary Metabolic Response
R832414C002 Endothelial Cell Responses to PM—In Vitro and In Vivo
R832414C003 Project 3 -- Inhalation Exposure Assessment of San Joaquin Valley Aerosol
R832414C004 Project 4 -- Transport and Fate Particles
R832414C005 Project 5 -- Architecture Development and Particle Deposition