Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage

Environ Health Perspect. 2003 Apr;111(4):455-60. doi: 10.1289/ehp.6000.

Abstract

The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aerosols
  • Air Pollutants / adverse effects*
  • Animals
  • Biological Assay
  • Epithelial Cells
  • Heme Oxygenase (Decyclizing) / biosynthesis*
  • Heme Oxygenase (Decyclizing) / pharmacology
  • Heme Oxygenase-1
  • Humans
  • Lung / cytology
  • Lung / pathology
  • Macrophages
  • Membrane Proteins
  • Mice
  • Mitochondria / pathology*
  • Mitochondria / physiology
  • Oxidative Stress*
  • Particle Size
  • Polycyclic Aromatic Hydrocarbons / adverse effects*
  • Reactive Oxygen Species

Substances

  • Aerosols
  • Air Pollutants
  • Membrane Proteins
  • Polycyclic Aromatic Hydrocarbons
  • Reactive Oxygen Species
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse