CARDIOVASCULAR CONSEQUENCES OF IMMUNE MODIFICATION BY TRAFFIC-RELATED EMISSIONS
Impact/Purpose:
Traffic-related emissions are associated with the incidence and progression of acute and chronic cardiovascular sequelae in human population studies. Such phenomena of near-roadway health effects have yet to be characterized toxicologically. Because of overlapping issues related to noise, socioeconomic status, ethnicity, etc, there is a need to better understand the biological plausibility that fresh mixtures of vehicular emissions have a more potent than expected impact on human health. We hypothesize that the complex mixtures produced by traffic are inherently more toxic due to the combined presence of both particulates and volatile organic emissions. Furthermore, we hypothesize that emissions-induced oxidation of certain endogenous phospholipids, presumably from the pulmonary surfactant, can stimulate the activity of immune cells through such receptors and in turn promote the invasion of existing vascular lesions.
Description:
Findings will 1) indicate the most potent combinations of urban roadway and background copollutants in terms of vascular toxicity and 2) detail the role of the immune system in mechanistically driving the systemic effects of inhaled pollutants.
Record Details:
Record Type:PROJECT(
ABSTRACT
)
Start Date:12/01/2010
Completion Date:11/30/2015
Record ID:
249300
Keywords:
CORONARY ARTERY DISEASE, OXIDIZED PHOSPHOLIPIDS, ATHEROSCLEROSIS, PARTICULATE MATTER, VOLATILE ORGANIC COMPOUNDS, CARBON MONOXIDE, OZONE,
Related Organizations:
Role
:OWNER
Organization Name
:LOVELACE RESPIRATORY RESEARCH INSTITUTE
Organization Name
:UW CCAR
Mailing Address
:2425 Ridgecrest Dr. SE
Citation
:Albuquerque
State
:NM
Zip Code
:87108
Role
:OWNER
Organization Name
:UNIVERSITY OF WASHINGTON
Organization Name
:UW CCAR
Mailing Address
:1410 NE Campus Parkway
Citation
:Seattle
State
:WA
Zip Code
:98195
Role
:OWNER
Organization Name
:UNIVERSITY OF NEW MEXICO
Organization Name
:UW CCAR
Citation
:Albuquerque
State
:NM
Zip Code
:87131
Project Information:
Approach
:This project will use complex roadway mixtures as generated and characterized in the laboratory. In Aim 1, we will ascertain 1) the potentiating effects of physical and photochemical aging on fresh emissions and 2) interactions of vehicular emissions with pertinent copollutants (ozone, road dust), both in terms of driving systemic vascular oxidative stress. In Aim 2, we will examine effects of the emissions-induced oxidative modifications to endogenous phospholipids, in terms of activating immune-modulating receptors such as LOX-1, CD-36, TLR-2, and TLR-4. This Aim will utilize transgenic models to examine the roles of these receptors, as well as characterize the lipidomic alterations in various tissues. Lastly, in Aim 3, we will further explore the role of specific immune cell populations as participants in the innate and adaptive responses to emissions-induced phospholipid modifications. In this Aim, we will utilize mouse models of immunodeficiency, including SCID and B-Cell deficient models. Additionally, we will pursue bone-marrow transplants from mice lacking those receptors described in Aim 2 to mechanistically establish the involvement of the oxidatively-modified phospholipids.
Cost
:$834,357.00
Research Component
:Health Effects
Project IDs:
ID Code
:R834796C003
Project type
:Center