Cellular Mechanisms of Pulmonary Inflammation by Environmental Particles

EPA Grant Number: R824790
Title: Cellular Mechanisms of Pulmonary Inflammation by Environmental Particles
Investigators:
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: October 1, 1995 through September 30, 1998
Project Amount: $546,895
RFA: Air Pollutants (1995) Recipients Lists
Research Category: Air Quality and Air Toxics , Air

Description:

This project investigates the mechanisms by which particulates within air pollution may cause significant morbidity and mortality at commonly encountered ambient concentrations. The underlying hypothesis of this proposal is that pre-existing pulmonary disease amplifies or 'primes' the response of lung macrophages and epithelial cells to inhaled particles, resulting in increased inflammation and health effects. We will use 'real-world' concentrated ambient air particles of both fine and ultrafine sizes in the following specific aims: 1) characterize the phlogistic effects of concentrated ambient particulates (CAPs) on lung cells 'primed' by inflammatory mediators; 2) characterize the effects of inhaled CAPs on pre-existing inflammatory lung disease using an in vivo asthma model; and 3) identify pathogenic components within concentrated ambient particles. We will first test our hypothesis using in vitro assays to measure production of reactive oxygen intermediates (ROI) and pro-inflammatory cytokines by normal or 'primed' lung macrophages and epithelial cells after uptake of CAPs. We will establish dose-response parameters for inflammatory priming agents, dose of particles and the cellular response. We will also test our hypothesis in vivo, comparing airway inflammation and function in normal or asthmatic rats exposed by inhalation to concentrated ambient particles. Our last aim is to identify using sophisticated ultrastructural and analytical techniques the pathogenic components within samples of ambient particulates. These studies will provide new and important mechanistic information about the pathogenesis of health effects from inhaled ambient particulates.

Publications and Presentations:

Publications have been submitted on this project: View all 10 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 9 journal articles for this project

Supplemental Keywords:

air, ambient air, atmosphere, tropospheric, health effects, animal, particulates, Massachusetts, MA, Region 1., RFA, Scientific Discipline, Air, Geographic Area, particulate matter, Health Risk Assessment, Environmental Chemistry, air toxics, State, Atmospheric Sciences, EPA Region, ambient aerosol, particle size, human health effects, concentrated ambient particulates (CAPs), morbidity, respiration, exposure and effects, pulmonary disease, epithelial cells, air pollution, Massachusetts (MA), cellular mechanisms, human exposure, lung inflammation, particulate exposure, inhaled, mortality, pathogenesis

Progress and Final Reports:

  • 1996
  • 1997
  • Final Report