Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions

EPA Grant Number: R834796C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834796
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: University of Washington Center for Clean Air Research
Center Director: Vedal, Sverre
Title: Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions
Investigators: Campen, Matthew J. , Lund, Amie K. , McDonald, Jacob D. , Rosenfeld, Michael
Current Investigators: Campen, Matthew J. , McDonald, Jacob D. , Rosenfeld, Michael
Institution: Lovelace Respiratory Research Institute , University of New Mexico , University of Washington
Current Institution: University of New Mexico , Lovelace Respiratory Research Institute , University of Washington , Washington State University
EPA Project Officer: Callan, Richard
Project Period: December 1, 2010 through November 30, 2015 (Extended to November 30, 2017)
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

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.

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.

Expected Results:

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.

Publications and Presentations:

Publications have been submitted on this subproject: View all 20 publications for this subprojectView all 172 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 13 journal articles for this subprojectView all 75 journal articles for this center

Supplemental Keywords:

coronary artery disease, oxidized phospholipids, atherosclerosis, particulate matter, volatile organic compounds, carbon monoxide, ozone,, Health, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, Air Quality, air toxics, Health Risk Assessment, Risk Assessments, mobile sources, Biochemistry, Environmental Monitoring, Risk Assessment, ambient air quality, particulate matter, atmospheric particulate matter, air pollutants, vehicle emissions, aerosol particles, motor vehicle emissions, air quality models, airway disease, bioavailability, motor vehicle exhaust, air pollution, particle exposure, atmospheric aerosols, ambient particle health effects, vascular dysfunction, cardiotoxicity, atmospheric chemistry, cardiovascular disease

Progress and Final Reports:

2011 Progress Report
2012 Progress Report
2013 Progress Report
2015 Progress Report
2016 Progress Report


Main Center Abstract and Reports:

R834796    University of Washington Center for Clean Air Research

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834796C001 Exposure Mapping – Characterization of Gases and Particles for ExposureAssessment in Health Effects and Laboratory Studies
R834796C002 Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies
R834796C003 Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions
R834796C004 Vascular Response to Traffic-Derived Inhalation in Humans
R834796C005 Effects of Long-Term Exposure to Traffic-Derived Particles and Gases on Subclinical Measures of Cardiovascular Disease in a Multi-Ethnic Cohort