Effects of Air Pollutant Particles and Their Components on Airway Host Defense

EPA Grant Number: U916167
Title: Effects of Air Pollutant Particles and Their Components on Airway Host Defense
Investigators: Klein-Patel, Marcia E.
Institution: University of Medicine and Dentistry of New Jersey
EPA Project Officer: Zambrana, Jose
Project Period: January 1, 2003 through January 1, 2006
Project Amount: $92,142
RFA: STAR Graduate Fellowships (2003) Recipients Lists
Research Category: Academic Fellowships , Biology/Life Sciences , Fellowship - Biochemistry, Molecular Biology, Cell Biology, Development Biology, and Genetics


The objective of this research project is to define the effects of acute and subacute exposure to environmental particles on the host's ability to evade infection. Poor ambient air quality is associated with an increased prevalence of respiratory infection in a population. However, its effects on various host defense mechanisms are poorly understood. Antimicrobial peptides are components of innate immunity, which are induced upon stimulation by bacteria, bacterial components, or inflammatory mediators. These include a class of conserved cationic peptides called defensins, which are widely distributed throughout many tissues and cell types and are microbicidal for bacteria, fungi, mycobacteria, and enveloped viruses. Preliminary studies in our laboratory with primary bovine tracheal epithelial cells (TEC) have found that short-term exposure with as little as 5.4 g/cm2 of residual oil fly ash (ROFA), a small particulate combustion emission collected downstream of an oil-burning power plant, causes a greater than 90 percent reduction in NF-B-activated ß-defensin expression. Therefore, I hypothesize that acute and subacute exposure to pollutants such as ROFA and urban particulate matter (UPM) can cause increased susceptibility to microbial pathogens by inhibiting expression of ß-defensins. Additionally, particulate pollutants may be mediating these effects through small particles or soluble components.


As a marker of the innate immune response, I will examine ß-defensins to determine how their expression and activity are altered by the presence of UPM. To understand the mechanism of these effects, I will elucidate the components of particulate airway pollution responsible for this phenomenon. Bovine TEC are a useful animal model for studying -defensin expression in response to pollution. Large quantities of tissue are readily available and are easily maintained in the laboratory and produce tracheal antimicrobial peptide (TAP), the bovine homolog of human ß-defensin 2 (HBD-2), which can be easily detected by molecular techniques. Using this approach, I aim to quantify the effect of acute and subacute exposure to ROFA and UPM on the production of TAP by lipopolysaccharide-stimulated TEC. The kinetics of this response will be defined, and I will examine the ability of airway surface fluid to kill bacterial pathogens subsequent to TEC pollutant exposure. Next, I will determine the components of ROFA and UPM that account for changes in the production of TAP in response to microbial products. Lastly, the in vivo response to acute and subacute particulate pollutant exposure will be quantified in a rodent model. The results of this research project will help define the immunotoxic mechanism of air pollution, and aid in the development of appropriate standards for environmental policy.

Supplemental Keywords:

fellowship, air pollution particles, airway host defense, conserved cationic peptides, defensins, tracheal epithelial cells, TEC, residual oil fly ash, ROFA, urban particulate matter, UPM, microbial pathogens, tracheal antimicrobial peptide, TAP.

Progress and Final Reports:

  • 2003
  • 2004
  • Final