Saber, Anne Thoustrup4; Lamson, Jacob Stuart4; Jacobsen, Nicklas Raun4; Ravn-Haren, Gitte1; Hougaard, Karin Sørig4; Nyendi, Allen Njimeri4; Wahlberg, Pia7; Madsen, Anne Mette4; Jackson, Petra4; Wallin, Håkan6; Vogel, Ulla Birgitte1
1 National Food Institute, Technical University of Denmark2 Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark3 Department of Micro- and Nanotechnology, Technical University of Denmark4 National Research Center for Working Environment5 Danish Technological Institute6 University of Copenhagen7 Danish Technological Institute
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.