title: Particle-induced pulmonary acute phase response correlates with neutrophil influx linking inhaled particles and cardiovascular risk.
abstract: 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.
authors.affiliation: The National Research Centre for the Working Environment, Copenhagen, Denmark. ats@nrcwe.dk
authors.forename: Anne Thoustrup
authors.initials: AT
authors.lastname: Saber
authors.forename: Jacob Stuart
authors.initials: JS
authors.lastname: Lamson
authors.forename: Nicklas Raun
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Gitte
authors.initials: G
authors.lastname: Ravn-Haren
authors.forename: Karin Sørig
authors.initials: KS
authors.lastname: Hougaard
authors.forename: Allen Njimeri
authors.initials: AN
authors.lastname: Nyendi
authors.forename: Pia
authors.initials: P
authors.lastname: Wahlberg
authors.forename: Anne Mette
authors.initials: AM
authors.lastname: Madsen
authors.forename: Petra
authors.initials: P
authors.lastname: Jackson
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology*; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D064347:Microscopy, Electrochemical, Scanning; D037742:Nanotubes, Carbon / Q000737:chemistry; D009504:Neutrophils / Q000276:immunology*; D000685:Serum Amyloid A Protein / Q000235:genetics; D053260:Soot / Q000633:toxicity; D014025:Titanium / Q000633:toxicity
chemical_list: D037742:Nanotubes, Carbon; D000685:Serum Amyloid A Protein; D053260:Soot; C009495:titanium dioxide; D014025:Titanium
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