Particle-induced pulmonary acute phase response correlates with neutrophil influx linking inhaled particles and cardiovascular risk

PLoS One. 2013 Jul 24;8(7):e69020. doi: 10.1371/journal.pone.0069020. Print 2013.


Background: Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk.

Methods: We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes.

Results: Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points.

Conclusions: Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / immunology*
  • Animals
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / metabolism
  • Female
  • Inhalation Exposure / adverse effects
  • Liver / drug effects
  • Liver / immunology
  • Liver / metabolism
  • Lung / drug effects*
  • Lung / immunology*
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electrochemical, Scanning
  • Nanotubes, Carbon / chemistry
  • Neutrophils / immunology*
  • Serum Amyloid A Protein / genetics
  • Soot / toxicity
  • Titanium / toxicity


  • Nanotubes, Carbon
  • Serum Amyloid A Protein
  • Soot
  • titanium dioxide
  • Titanium

Grants and funding

The Danish Working Environment Research Fund supported the study (NanoKem, grant #20060068816 and NanoPlast, grant 22-2007-03 and Danish Centre for Nanosafety grant 20110092173/3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.