Determinants of the proinflammatory action of ambient particulate matter in immortalized murine macrophages

Environ Health Perspect. 2010 Dec;118(12):1728-34. doi: 10.1289/ehp.1002105. Epub 2010 Jul 27.

Abstract

Background: Proximity to traffic-related pollution has been associated with poor respiratory health in adults and children.

Objectives: We wished to test the hypothesis that particulate matter (PM) from high-traffic sites would display an enhanced capacity to elicit inflammation.

Methods: We examined the inflammatory potential of coarse [2.5-10 µm in aerodynamic diameter (PM(2.5-10))] and fine [0.1-2.5 µm in aerodynamic diameter (PM(0.1-2.5))] PM collected from nine sites throughout Europe with contrasting traffic contributions. We incubated murine monocytic-macrophagic RAW264.7 cells with PM samples from these sites (20 or 60 µg/cm²) and quantified their capacity to stimulate the release of arachidonic acid (AA) or the production of interleukin-6 and tumor necrosis factor-α (TNFα) as measures of their inflammatory potential. Responses were then related to PM composition: metals, hydrocarbons, anions/cations, and endotoxin content.

Results: Inflammatory responses to ambient PM varied markedly on an equal mass basis, with PM(2.5-10) displaying the largest signals and contrasts among sites. Notably, we found no evidence of enhanced inflammatory potential at high-traffic sites and observed some of the largest responses at sites distant from traffic. Correlation analyses indicated that much of the sample-to-sample contrast in the proinflammatory response was related to the content of endotoxin and transition metals (especially iron and copper) in PM(2.5-10). Use of the metal chelator diethylene triamine pentaacetic acid inhibited AA release, whereas recombinant endotoxin-neutralizing protein partially inhibited TNFα production, demonstrating that different PM components triggered inflammatory responses through separate pathways.

Conclusions: We found no evidence that PM collected from sites in close proximity to traffic sources displayed enhanced proinflammatory activity in RAW264.7 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / toxicity*
  • Animals
  • Arachidonic Acid / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Inflammation Mediators / metabolism
  • Macrophages / drug effects*
  • Mice
  • Particle Size
  • Particulate Matter / toxicity*
  • Pentetic Acid / toxicity
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Air Pollutants
  • Inflammation Mediators
  • Particulate Matter
  • Tumor Necrosis Factor-alpha
  • Arachidonic Acid
  • Pentetic Acid