Grantee Research Project Results

2003 Progress Report: Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats

EPA 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: Health Effects Institute (2000 — 2005)
Center Director: Greenbaum, Daniel S.
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, 2003 through May 31, 2004
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Particulate Matter , Air Quality and Air Toxics , Air

Objective:

The objectives of this research project are to: (1) determine whether particle size influences particulate matter (PM)-induced alterations in the handling (i.e., uptake and/or killing) of an ongoing pulmonary infection with Streptococcus pneumoniae; (2) identify whether the soluble or insoluble portion of a given size fraction of ambient air PM is responsible for the exacerbation of an ongoing pneumococcal-associated pneumonia; and (3) ascertain which transition metals (either individually or in combination), found most active in the previously identified portion of ambient PM, play significant roles in exacerbating ongoing pneumococcal-induced pneumonia in PM-exposed hosts.

Previous studies performed in this laboratory have demonstrated that ambient PM exposure worsens the outcome of S. pneumoniae-associated pneumonia in rats. Although the aforementioned findings are compelling and provide a strong basis for the current studies, the question remains as to which factors and/or individual PM constituents are responsible for producing the observed effects on pulmonary host resistance against infectious bacteria. Thus, these studies correlate the physical-chemical attributes of ambient PM with its in vivo immunotoxicity, so as to identify and characterize the role of particle form (i.e., soluble vs. insoluble), size (i.e., coarse, fine, ultrafine), and constitutive transition metals on the ability of the particle to exacerbate an ongoing S. pneumoniae infection. This and related questions must be answered to better understand the mechanism(s) by which PM may act to increase morbidity and/or mortality in exposed individuals.

The central hypothesis of this study was that particle size and solubility play a critical role in mediating PM-associated pneumonia-related morbidity/mortality in exposed individuals. Moreover, any PM-induced changes in the ability of the host to “handle” infectious pneumonia-producing agents are likely because of, at least in part, the transition metals (either individually or in combination) associated with inhaled particulates. By exposing rats previously infected with S. pneumoniae (i.e., 48 hours prior to PM exposure) to ambient particles of varying size ranges and solubilities or to chemically characterized constituents of ambient PM, individual physical-chemical attributes that influence the ability of PM to alter host resistance against infectious agents can be defined.

This is one of the projects funded by the New York University (NYU) PM Center. The progress for the other projects is reported separately (see reports for R827351C001 through R827351C006, and R827351C008 through R827351C016).

Progress Summary:

Little progress has been made on this project in the past year because of extensive personnel limitations that included maternity leave and the resignation of the project’s only full-time equivalent. Moreover, the newly hired employee resigned the position prior to job commencement and left after working for only 2 weeks. A new technician has been hired, as of early June, and she has begun training with the generation and exposure system.

Despite serious personnel issues, some progress has been made regarding the generation system. The system has been modified such that metal concentrations in the nanogram range (i.e., 80-100 ng/m³) can be generated and inhaled (nose only) by exposed rats. The system currently is being validated and particle concentrations assured by graphite furnace atomic spectroscopy.

Future Activities:

The first study will entail (nose-only) inhalation exposure of S. pneumoniae infected to 100 ng Fe/m³ and is anticipated to commence in August.

Journal Articles on this Report : 1 Displayed | Download in RIS Format

Publications Views
Other subproject views:	All 3 publications	2 publications in selected types	All 2 journal articles
Other center views:	All 112 publications	101 publications in selected types	All 89 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	Zelikoff JT, Chen LC, Cohen MD, Fang K, Gordon T, Li Y, Nadziejko C, Schlesinger RB. Effects of inhaled ambient particulate matter on pulmonary antimicrobial immune defense. Inhalation Toxicology 2003;15(2):131-150.	R827351 (Final) R827351C007 (2003) R827351C007 (Final)	Abstract from PubMed Full-text: Berkeley-Full Text PDF Exit Abstract: Taylor and Francis-Abstract Exit

Supplemental Keywords:

thoracic particles, PM₁₀, fine particles, PM_2.5, ultrafine particles, PM _0.1, lung dosimetry models, human exposure models, pulmonary responses, cardiovascular responses, immunological responses, criteria air pollutants, concentrated ambient aerosols, aerosol, air pollutants, air pollution, airborne pollutants, airway disease, airway inflammation, airway variability, allergen, ambient air, ambient air quality, analytical chemistry, assessment of exposure, asthma, asthma morbidity, atmospheric monitoring, biological markers, childhood respiratory disease, children, combustion, combustion contaminants, combustion emissions, compliance monitoring, dosimetry, epidemiology, exposure, exposure and effects, health effects, heart rate variability, human exposure, human health, human health effects, incineration, lead, lung, mercury, morbidity, particulates, pulmonary, pulmonary disease, respiratory,, RFA, Health, Air, Scientific Discipline, PHYSICAL ASPECTS, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Physical Processes, Risk Assessments, particulate matter, Environmental Chemistry, Analytical Chemistry, Atmospheric Sciences, Toxicology, Environmental Monitoring, Risk Assessment, epidemelogy, chemical characteristics, pneumonia, aerosol composition, airborne particulate matter, human exposure, ambient air monitoring, environmental risks, acute lung injury, metal absorption, atmospheric particles, atmospheric aerosol particles, particulates, PM, exposure, atmospheric particulate matter, ambient air quality, air pollution, human health risk, acute cardiovascular effects, air toxics, Sulfur dioxide

Relevant Websites:

http://www.med.nyu.edu/environmental/centers/epa/ Exit

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R827351 Health Effects Institute (2000 — 2005)

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 PM_2.5
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 PM_2.5 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 PM_2.5
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

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.