2000 Progress Report: Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status

EPA Grant Number: R827351C008
Subproject: this is subproject number 008 , 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: Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
Investigators: Cohen, Mitchell
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

Objective:

The objective of this research project is to reveal which of the many metals present in PM (alone or in combination) might be responsible for any effects on leukocyte function, or the mechanism(s) of action underlying these effects. Epidemiological studies show that PM induces/exacerbates infectious lung disease (e.g., pneumonia), and toxicological studies show that PM can alter the manner by which the lungs handle bacterial infections. Metals, a major component of PM, are a class of toxicants known to be immunomodulatory. Several metals produce effects upon directly-exposed immune cells (i.e., pulmonary macrophages (PAM) and pulmonary neutrophils (PMN)) that decreases their antibacterial activities in the lungs.

Progress Summary:

One metal commonly present in PM is iron (Fe), an important micronutrient for both the growth of bacteria in situ as well as for maintenance of PAM and PMN antibacterial function. Research this year has focused on two propositions, that: (1) PM modulates the antibacterial function of lung phagocytes by altering their intracellular Fe status, in part, by affecting homeostatic mechanisms that assure tight control of cellular Fe levels so as to permit optimal antibacterial activity; and (2) the relative (with respect to other metals present) content of Fe in PM governs whether this alteration involves either a direct effect or an indirect subversion of these mechanisms. For example, in PM with a high relative content of Fe, uptake/slow dissolution of insoluble Fe from PM in conjunction with increased cellular deposition of soluble Fe (due to normal lacto- (LF) or transferrin (T) activity) will lead to Fe overload in leukocytes and decreased antibacterial function. Conversely, in PM containing a low/very low Fe content, the presence of relatively greater amounts (with respect to Fe itself) of three major potential competitors for intrapulmonary LF-/T -binding (e.g., aluminum (Al), manganese (Mn), and vanadium (V)) will bring about a state of intracellular Fe deficit and reduced antibacterial function as a result of inhibited transport of endogenous Fe to PAM/PMN.

Future Activities:

Particulate matter (PM2.5) with varying metal contents will be obtained with cooperation from PM Centers in Los Angeles and Seattle; PM2.5 particles will be collected onto filters held in dichotomous samplers. The resulting filters from each site will be subdivided, pooled, and analyzed for two major objectives: (1) to determine the Fe status of PAM and PMN isolated from lungs of rats instilled with regional PM; and (2) to assess whether regional PM-related changes in PAM/PMN intracellular Fe status can give rise to modifications in their antibacterial function.

All regional PM samples will be characterized for respective Fe, Al, Mn, and V content. This information will be critical in validating the role that content relationship among these LF-/T-binding metals in the samples may have in the mechanism(s) underlying effects on leukocyte Fe status and anti-bacterial function. Furthermore, this data will permit future studies, wherein artificially-generated PM2.5 containing only Al, Fe, Mn, and V at the levels present in each sample are instilled into rats and the timeframe and magnitude of any effect upon PAM/PMN Fe status/antibacterial function assessed, to verify that it is the metals in each regional sample (rather than organics, endotoxin, etc.) that are responsible for any observed effects.

Journal Articles:

No journal articles submitted with this report: View all 5 publications for this subproject

Supplemental Keywords:

particulate matter, PM, exposure, epidemiology, toxicology, metals, pulmonary macrophage, pulmonary neutrophil, leukocyte, Los Angeles, California, CA, Seattle, Washington, WA., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Analytical Chemistry, Environmental Monitoring, Physical Processes, Atmospheric Sciences, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, lung injury, metal absorption, air toxics, atmospheric particles, chemical characteristics, toxicology, ambient air monitoring, acute lung injury, airborne particulate matter, environmental risks, exposure, epidemelogy, Sulfur dioxide, air pollution, pneumonia, leukocyte function, aerosol composition, atmospheric aerosol particles, human exposure, PM, exposure assessment, human health risk, metals

Progress and Final Reports:

Original Abstract
  • 1999
  • 2001 Progress Report
  • 2002 Progress Report
  • 2003 Progress Report
  • 2004
  • Final Report

  • 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