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

Anne Thoustrup Saber, Jacob Stuart Lamson, Nicklas Raun Jacobsen, Gitte Ravn-Haren, Karin Sørig Hougaard, Allen Njimeri Nyendi, Pia Wahlberg, Anne Mette Madsen, Petra Jackson, Håkan Wallin, Ulla Birgitte Vogel

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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.

Original languageEnglish
Article numbere69020
JournalPloS one.
Volume8
Issue number7
ISSN1932-6203
DOIs
Publication statusPublished - 2013

Bibliographical note

Copyright: 2013 Saber et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.

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