Impact/Purpose:

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.

Description:

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.

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Project Information:

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.

Cost :$.00

Research Component :Health Effects

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