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2006 Progress Report: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
EPA Grant Number: R832414Center: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Center Director: Wexler, Anthony S.
Title: San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Investigators: Wexler, Anthony S. , Fanucchi, Michelle V. , Pinkerton, Kent E. , Wilson, Dennis
Current Investigators: Wexler, Anthony S. , Pinkerton, Kent E.
Institution: University of California - Davis
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: October 1, 2005 through September 30, 2010
Project Period Covered by this Report: October 1, 2005 through September 30, 2006
Project Amount: $7,999,767
RFA: Particulate Matter Research Centers (2004)
Research Category: Particulate Matter
Description:
Objective:This research investigates the mechanistic links between ambient particles and health effects. This objective includes two goals: (1) understanding the metabolic response of tissue and organs when they are exposed to particulate pollutants; and (2) understanding the characteristics of the particulate pollutants and their gaseous co-pollutants that elicit these responses. Five projects are underway at the Center. The projects investigate the metabolic response to pollutant exposure in pulmonary and cardiovascular tissues, whole animal effects of exposure, transport of particles from the airways to other tissues, and the effects of particles and gases on lung development in juveniles.
Both field and laboratory studies are being performed. The field studies take place in the San Joaquin Valley of California, one of the worst violators of the National Ambient Air Quality Standards for particulate matter. UC Davis is located at the northern end of the San Joaquin Valley which facilitates this work. The laboratory studies at UC Davis examine the effects of particles from ambient sources and laboratory-generated particles with carefully controlled properties that model ambient ones or those from dominant sources. The research team is composed of physiologists, toxicologists, chemists, and engineers who already collaborate on air pollution studies in the UC Davis Air Quality Research Center. The SAHERC researchers are investigating a complementary set of hypotheses related to the mechanisms and loci of action that cause acute and chronic responses in normal animal models of children and adults and those made susceptible by exposure to particles and ozone during development.
The San Joaquin Valley (SJV) is an ideal location to study the nexus of air pollutants and their health effects because its residents are exposed to some of the worst particulate air pollution in the country, community health effects are evident. Air-quality–related health indicators reflect the severity of the region’s air quality problems; for example, asthma and cardiovascular disease rates are some of the highest in the country. The San Joaquin Valley routinely experiences some of the highest fine airborne particulate matter concentrations in the U.S., with fine and ultrafine particle concentrations that rival those found in Los Angeles. The American Lung Association reports that three of the four most polluted American cities are located in the SJV. Many of the air pollution source categories in the SJV are the same as in the rest of the country: transportation, wood smoke, refineries, and agriculture. The Valley also encompasses sharp gradients—concentrations are higher in the south-central portion of the valley and significantly lower in the foothills and further north; there is a seasonal variation in the concentrations as well.
The AQRC at UC Davis has research investigations underway ranging from biological effects of air pollution to global climate research. The scientists on the AQRC team who are working on this project investigate pulmonary and cardiovascular biology and aerosol and atmospheric science, working together to examine urban and regional smog and its health effects. UC Davis has one of the largest concentrations of university faculty with air pollution expertise at any one campus in the U.S. with over 70 faculty members on campus involved in air quality research and affiliated with the AQRC at UC Davis.
Progress Summary:This is a general progress report for the SAHERC. The progress for the specific research projects conducted by the Center is reported separately.
All studies in the SAHERC are being undertaken within the primary theme of ‘ambient particulate matter and resulting health effects in the San Joaquin Valley.’ Below is a chart outlining the center’s five projects. All five research projects are complementary and focus on the role of particulates in pulmonary and cardiovascular health effects. The research progress for these studies is summarized below in a paragraph for each project.
Project 1—Pulmonary Metabolic Response
Principal Investigator: Michelle Fanucchi
Co-Investigators: Charles Plopper, Alan Buckpitt
First, to evaluate the acute effects of particulate exposure in rats, validated the use of a dry powder insufflator as a consistent method for acute, intrapulmonary delivery of 1 to 5 mg of particulates evenly throughout the airways. Second, we validated a strategy to systematically define the impact that individual components of particulate matter have on the cytotoxicity of airway epithelium. We found that carbon particles not coated with 1-nitronaphthalene did not cause any appreciable cellular injury to airway epithelium and that the majority of the particles were cleared from the airways within 2 hours. However, particles coated with 1-nitronaphthalene caused focal areas of exfoliation and cellular injuries in all airways evaluated (proximal, mid-level and distal airways) and were not completely cleared from the airways.
Project 2—Endothelial Cell Responses to PM—In Vitro and In Vivo
Principal Investigator: Dennis Wilson
Co-Investigator: John Rutledge
We concentrated on signaling responses associated with oxidant stress using laboratory generated particles as well as historically archived (NIST) environmental particles until ambient particulate matter from the San Joaquin Valley are collected. We also performed several experiments evaluating culture exposure methods that will best recapitulate expectations of exposure conditions in vivo.
Project 3—Inhalation Exposure Assessment of San Joaquin Valley Aerosol
Principal Investigator: Kent Pinkerton
Co-Investigators: Mike Kleeman, Ann Bonham, John Rutledge
We constructed the prototype insert for holding individual mice in the exposure chamber and conducted preliminary CAPs exposure where 24 hr ECG signals were recorded for HRV analysis using an implanted ECG telemetry system. We are currently analyzing these data. Samples of airborne particulate matter were collected during the week of October 31 – November 4, 2005 and November 7 – November 11, 2005 each day from 9am – 3pm to coincide with animal exposure periods. The PM1.8 mass and Ultrafine (PM0.1) concentrations were significantly lower than concentrations experienced during typical air pollution events in the SJV. Organic carbon, elemental carbon, and water soluble ions (sulfate, nitrate, etc) made up only a very small fraction of the particle mass collected during sampling. This contrasts sharply with previous samples collected during the winter in the SJV where carbon and water soluble ions made up the majority of the particle mass. Elemental analysis of these samples will be conducted in the following weeks.
Project 4—Transport Mechanisms and Systemic Fate of Inspired Ultrafine Particles
Principal Investigator: Dennis Wilson
Co-Investigators: Angelique Louie, Michelle Fanucchi, Ian Kennedy, Charles Plopper, Alan Buckpitt
Nanoparticles can be successfully labeled with copper by pre-incubation of copper with p-SCN-Bz-DOTA followed by immediate conjugation of the p-SCN-Bz-Cu-DOTA to aminated polystyrene beads in a tetramethylammonium phosphate buffer. Whole animal imaging studies in the first reporting period were limited by the challenges of particle conjugation. Given the difficulties in creating the Cu64 conjugates, we also evaluated the potential for using intravital fluorescence as an imaging modality in these studies. Results of this study showed significant background autofluorescence in the whole animal but that fluorescent signal could be detected in dissected tissues. Unfortunately this initial experiment resulted in intraesophageal instillation but did offer proof of concept for potential future studies using florescence labeled particles in isolated organs.
Project 5—Architecture Development and Particle Deposition
Investigators: Anthony Wexler and Charles Plopper
Two current activities are highlighted, acquisition of CT image data, and second, characterization of pulmonary architecture. First, a custom designed micro CT scanner was used to obtain voxel based images of lung casts. The 3D CT data set was reconstructed from 1000 projections with a custom developed cone beam reconstruction program using Feldkamp-Davis-Kress (FDK) algorithm. Second, we developed a new algorithm to quantify the branching structure of the pulmonary tree. This algorithm was able to successfully analyze airway radii as small as 2 voxels. The algorithm was validated by error analysis and comparison of statistical results obtained by comparing our technique with previous anatomy studies of rat lung (Phillips 1995, Sera 2003).
Future Activities:Planned activities for the next reporting period are described by project below.
Project 1—Pulmonary Metabolic Response
Since, the initial experiments did not indicate a strong dose-response relationship between the amount of 1-nitronaphthalene coated on the particles and the amount of injury present in the airways, we will reduce the amount of 1-nitronapthalene per particle. Also, we will investigate whether it is the concentration of the PAH on individual particles or the total PAH concentration administered that is important in particle toxicity, and whether the type of core particle affects the toxicity. Future studies will utilize flame-generated soot doped with 1-nitronaphthalene. In addition, ambient particles from urban and rural sites in the San Joaquin Valley will be assessed for their cytotoxicity. The samples with the greatest cytotoxicity will be analyzed for PAH concentrations. The laboratory generated particles will then be adjusted to contain PAH’s relevant to those found in San Joaquin Valley samples.
Project 2—Endothelial Cell Responses to PM—In Vitro and In Vivo
In the next project year we plan to apply our ROS signaling assays to evaluate responses to SJV derived PM in cultured human aortic and pulmonary artery endothelium. We will evaluate potential approaches to ROS detection with ESR as an alternative to dye based assays. We plan to complete the proposed evaluation of TGFb family signaling in response to PM as well as the proposed evaluation of PM effects on endothelial barrier function.
Project 3—Inhalation Exposure Assessment of San Joaquin Valley Aerosol
For the next reporting period, our plan is to (1) continue with exposures in the late summer season (i.e., September); (2) conduct CAPs experiments in our designated urban site of the San Joaquin Valley (Fresno); (3) analyze the HRV, particle concentration and composition, stress test results; and (4) conduct patch-clamping analysis of identified cardiac vagal neurons.
Project 4—Transport Mechanisms and Systemic Fate of Inspired Ultrafine Particles
In the next year we plan to focus on the blood kinetics of indium labeled particles while continuing development of our PET imaging studies. Key to the latter will be consistent labeling of synthetic ultrafine particles with Cu60 as this has been the most significant challenge in our initial year. We are also exploring the option of Xenogen based fluorescence imaging as a developmental tool that does not require the use of radiochemicals. We will continue our transcellular transport studies in cultured endothelial cells using fluorescence tagged particles in concert with dual labeling for caveolar proteins.
Project 5—Architecture Development and Particle Deposition
We will continue to improve the algorithm so as to clearly distinguish erroneous data from reliable results. In addition we will try various optimization subroutines to reduce computer analysis time. We will characterize normal architecture geometric parameters and their normal variations in adult rats before commencing with ozone and ozone+PM exposures.
Journal Articles: 10 Displayed | Download in RIS Format
| Other center views: | All 19 publications | 10 publications in selected types | All 10 journal articles |
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Day KC, Plopper CG, Fanucchi MV. Age-specific pulmonary cytochrome P-450 3A1 expression in postnatal and adult rats. American Journal of Physiology-Lung Cellular and Molecular Physiology 2006;291(1):L75-L83. |
R832414C001 (2007) R832414C001 (2008) |
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Donaldson K, Borm PJA, Oberdorster G, Pinkerton KE, Stone V, Tran CL. Concordance between in vitro and in vivo dosimetry in the proinflammatory effects of low-toxicity, low-solubility particles:the key role of the proximal alveolar region. Inhalation Toxicology 2008;20(1):53-62. |
R832414C003 (2008) |
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Kennedy IM. The health effects of combustion-generated aerosols. Proceedings of the Combustion Institute 2007;31(2):2757-2770. |
R832414C001 (2008) |
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Kleeman MJ, Riddle SG, Jakober CA. Size distribution of particle-phase molecular markers during a severe winter pollution episode. Environmental Science & Technology 2008;42(17):6469-6475. |
R832414C003 (2008) |
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Lee DY, Wexler AS, Fanucchi MV, Plopper CG. Expiration rate drives human airway design. Journal of Theoretical Biology 2008;253(2):381-387. |
R832414C005 (2008) |
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Lee D, Park SS, Ban-Weiss GA, Fanucchi MV, Plopper CG, Wexler AS. Bifurcation model for characterization of pulmonary architecture. Anatomical Record 2008;291(4):379-389. |
R832414C005 (2008) |
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Lee D, Fanucchi MV, Plopper CG, Fung J, Wexler AS. Pulmonary architecture in the conducting regions of six rats. Anatomical Record 2008;291(8):916-926. |
R832414C005 (2008) |
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Riddle SG, Robert MA, Jakober CA, Hannigan MP, Kleeman MJ. Size-resolved source apportionment of airborne particle mass in a roadside environment. Environmental Science & Technology 2008;42(17):6580-6586. |
R832414C003 (2008) |
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Smith KR, Veranth JM, Kodavanti UP, Aust AE, Pinkerton KE. Acute pulmonary and systemic effects of inhaled coal fly ash in rats:comparison to ambient environmental particles. Toxicological Sciences 2006;93(2):390-399. |
R832414C003 (2006) R832414C003 (2007) R832414C003 (2008) |
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Tebockhorst S, Lee DY, Wexler AS, Oldham MJ. Interaction of epithelium with mesenchyme affects global features of lung architecture:a computer model of development. Journal of Applied Physiology 2007;102(1):294-305. |
R832414C005 (2007) R832414C005 (2008) |
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ambient air, ozone, exposure, health effects, human health, metabolism, sensitive populations, infants, children, PAH, metals, oxidants, agriculture, transportation,
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ENVIRONMENTAL MANAGEMENT, Air, Scientific Discipline, Health, RFA, PHYSICAL ASPECTS, Risk Assessment, Risk Assessments, Health Risk Assessment, Physical Processes, Biochemistry, particulate matter, Environmental Chemistry, exposure assessment, cardiovascular disease, chemical characteristics, particulate matter components, cardiopulmonary responses, human health risk, acute cardiovascular effects, human health effects, atmospheric particulate matter, exposure, airborne particulate matter, human exposure, PM
Relevant Websites:
Progress and Final Reports:
Original Abstract
2007 Progress Report
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