1999 Progress Report: Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed RatsEPA Grant Number: R827351C007
Subproject: this is subproject number 007 , established and managed by the Center Director under grant R827351
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: EPA NYU PM Center: Health Risks of PM Components
Center Director: N/A
Title: Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
Investigators: Zelikoff, Judith T.
Institution: New York University School of Medicine
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 1999 through May 31, 2000
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Based on the results of earlier studies, bacterial clearance from the lungs will be the biological endpoint used throughout these studies to evaluate the role of various physicochemical characteristics of particulate matter (PM) on disease exacerbation. The hypothesis of the originally proposed study was that particle size, solubility, and/or metal constituents play a critical role in mediating PM-associated, pneumonia-related morbidity/mortality in exposed individuals. By exposing rats already infected with Streptococcus pneumoniae to ambient particles of varying sizes or to their major metal constituents (in their soluble or insoluble forms) individually and in combination, individual physicochemical attributes that influence the ability of PM to alter host resistance against infectious agents could be defined.
The original objectives of this research project to test the above hypothesis were to: (1) determine whether particle size influences PM-induced alterations in the handling (i.e., uptake and/or killing) of an ongoing pulmonary infection with S. pneumoniae; (2) characterize the composition of those particles within that most immunomodulating size fraction of PM by determining the relative content, as well as their distribution between soluble and insoluble forms, of individual transition metals; and (3) determine, using artificially generated atmospheres, the role that solubility and concentration of the most prevalent metals present in the immunoreactive PM fraction might play in the observed exacerbation of pneumococcal-induced pneumonia.
As a result of problems in collection of different size particles without an extensive output of time and money, as well as problems with the concentrator to be used in this study, the originally proposed experiments for this project had to be redesigned. The research project now seeks to test the hypothesis that particle solubility, and/or metal constituents of PM, play a critical role in mediating PM-associated, pneumonia-related morbidity/mortality in exposed individuals. In this case, the role of metals (alone and in combination with each other), as well as the individual physicochemical attributes of the metals that influence the ability of PM to alter host resistance against infectious agents, can be defined. The amended proposal contains two specific objectives:
- We will characterize the composition of metal particles on PM by determining their relative content as well as their distribution between soluble and insoluble forms. Because New York City (NYC) studies cannot be performed at this time because of the lack of a “workable” concentrator, the role of solubility and the identification/quantitation of metal constituents in concentrated PM will be determined from NYC filter samples collected previously for another Health Effects Institute (HEI) study.
- We will determine the role that solubility and concentration of the most prevalent metals present in the immunoreactive PM fraction might play in the observed exacerbation of pneumococcal-induced pneumonia using artificially generated atmospheres. The identification/quantitation of transition metals from the previously collected filters will serve as a guide for the laboratory studies proposed in this objective. In this same objective, already infected animals will be exposed in the laboratory to either soluble or insoluble transition metals (i.e., Zn, Ni, Fe, Cu, or Mn) at a concentration relevant to that found in NYC air. For these laboratory studies, additional experiments examining the effects of metals inhaled prior to S. pneumoniae infection also will be conducted to determine whether exposure to PM before infection fails to affect host resistance.
A redesign of this project necessitated the investigators to design and build new generation/exposure units. Because of the toxicity/carcinogenicity of some of the selected metals, these units were built within individual exposure chambers. This part of the project is complete.
The second phase required the generation system to be tested and validated using several of the proposed metals. This has been accomplished, and the concentration fluctuations over time within a given chamber, as well as between chambers, are within expected ranges. The size of the generated soluble metals were determined using a cascade impactor, and they were found to be within the fine-sized range.
To determine relevant metal concentrations to use in these studies, NYC air particulates will be collected on filters and extracted. We will determine the concentrations of five metals (Zn, Mn, Cu, Fe, and Ni) that have been shown in previous air pollution studies to be associated with PM using graphite furnace atomic absorption spectroscopy.
We will examine the immunological, histological, and biochemical changes associated with a single 5-hour inhalation exposure to FeCl2 at a concentration of approximately 100 µg/m3 in studies employing uninfected 8-month-old F-344 rats. Effects will be examined 1, 18, and 48 hours post-metal exposure.
In another series of studies, we will infect rats with S. pneumoniae 48 hours prior to either air or Fe exposure. Rats will be sacrificed either just before initiation of exposure or 18 hours after exposure, and effects upon circulating blood cell profile and pulmonary bacterial burdens will be determined. Also, uninfected or S. pneumoniae-infected rats will be exposed for 5 hours to MnCl2 at a concentration of approximately 100 µg/m3.
Journal Articles:No journal articles submitted with this report: View all 3 publications for this subproject
Supplemental Keywords:thoracic particles, particulate matter, PM, PM10, fine particles, PM2.5, ultrafine particles, PM0.1, lung dosimetry models, human exposure models, pulmonary responses, cardiovascular responses, immunological responses, criteria air pollutants, concentrated ambient aerosols, air, health, waste, biochemistry, biology, chemical engineering, chemistry, children’s health, civil engineering, environmental engineering, environmental chemistry, physics, analytical chemistry, epidemiology, health risk assessment, immunology, incineration, combustion, combustion contaminants, combustion emissions, air toxics, tropospheric ozone, aerosol, air pollutants, air pollution, airborne pollutants, airway disease, airway inflammation, airway variability, allergen, ambient air, ambient air quality, assessment of exposure, asthma, asthma morbidity, atmospheric monitoring, biological markers, childhood respiratory disease, children, compliance monitoring, dosimetry, exposure, exposure and effects, health effects, heart rate variability, human exposure, human health, human health effects, lead, lung, mercury, morbidity, pulmonary, pulmonary disease, respiratory, animal, rat, toxicology, metal, pneumonia, Streptococcus pneumoniae, immunotoxic, sulfur dioxide, acute cardiovascular effects, acute lung injury, aerosol composition, air toxics, airborne particulate matter, ambient air monitoring, ambient air quality, atmospheric aerosol particles, atmospheric particles, atmospheric particulate matter, chemical characteristics, environmental risks, exposure assessment, human health risk, particulates,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Toxicology, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Analytical Chemistry, Environmental Monitoring, Physical Processes, Atmospheric Sciences, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, metal absorption, air toxics, atmospheric particles, chemical characteristics, ambient air monitoring, acute cardiovascular effects, acute lung injury, airborne particulate matter, environmental risks, exposure, epidemelogy, Sulfur dioxide, air pollution, pneumonia, aerosol composition, atmospheric aerosol particles, human exposure, PM, exposure assessment
Progress and Final Reports:Original Abstract
Main Center Abstract and Reports:R827351 EPA NYU PM Center: Health Risks of PM Components
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827351C001 Exposure Characterization Error
R827351C002 X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
R827351C003 Asthma Susceptibility to PM2.5
R827351C004 Health Effects of Ambient Air PM in Controlled Human Exposures
R827351C005 Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
R827351C006 Effects of Particle-Associated Irritants on the Cardiovascular System
R827351C007 Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
R827351C008 Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
R827351C009 Health Risks of Particulate Matter Components: Center Service Core
R827351C010 Lung Hypoxia as Potential Mechanisms for PM-Induced Health Effects
R827351C011 Urban PM2.5 Surface Chemistry and Interactions with Bronchoalveolar Lavage Fluid (BALF)
R827351C012 Subchronic PM2.5 Exposure Study at the NYU PM Center
R827351C013 Long Term Health Effects of Concentrated Ambient PM2.5
R827351C014 PM Components and NYC Respiratory and Cardiovascular Morbidity
R827351C015 Development of a Real-Time Monitoring System for Acidity and Soluble Components in Airborne Particulate Matter
R827351C016 Automated Real-Time Ambient Fine PM Monitoring System