Particle-Induced Pulmonary Acute Phase Response Correlates with Neutrophil Influx Linking Inhaled Particles and Cardiovascular Risk

Abstract

BackgroundParticulate 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.MethodsWe 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.ResultsPulmonary 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.ConclusionsPulmonary 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.

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

“…Doses and time points were selected based on the previous and ongoing studies in our group (Bourdon et al, 2012b;Husain et al, 2013;Jacobsen et al, 2009;Poulsen et al, 2013;Saber et al, 2012Saber et al, , 2013. The consistency in doses and time points across many studies enabled comparison of responses after exposure to different nanomaterials.…”

Occupational exposure during handling and loading of halloysite nanotubes – A case study of counting nanofibers

“…Unmodified HNTs have shown to induce very low cytotoxicity in the following human cell types: carcinoma cells, peripheral blood lymphocytes, primary umbilical vein endothelial cells, intestinal cells, and epithelial cells (Ahmed et al, 2015;Vergaro et al, 2010;Nan et al, 2008;Lai et al, 2013). However, as HNTs have similar dimensions as short carbon nanotubes (CNTs), they may potentially cause pulmonary inflammation and acute phase response following pulmonary exposure as previously reported for CNTs (Saber et al, 2013(Saber et al, , 2014Poulsen et al, 2015Poulsen et al, , 2017Jaurand, 2017).…”

A perspective on the developmental toxicity of inhaled nanoparticles

“…Of the estimated inhaled dose of 840 g of TiO 2 , approximately 30% reached and persisted in the maternal lung tissue until weaning. The particles caused persistent inflammation in the maternal airways, still present 3 weeks after termination of exposure, as well as acute phase response [9,73,92,93]. Exposure was not associated with effects on gestational or lactation parameters (maternal weight gain, gestation length, litter size, sex distribution, birth and lactation weights, implantations and loss thereof) [9].…”

“…Neither the particles nor the inflammatory condition need to be confined to the lungs. Particles may translocate and inflammatory mediators may be released into the systemic circulation [72,73] and transported to organs of importance for pregnancy and fetal development, e.g., the maternal neuro-endocrine circuits, placenta, uterus, and fetus. It is of interest, that systemically available NP may be taken up by placental cells and interfere indirectly with fetal development by inducing oxidative stress and inflammation therein.…”

“…The highest dose level was calculated to correspond to the lung deposition in the inhalation study described above [10]. In both studies, exposure induced inflammation and acute phase response in the lungs of the females, but did not affect gestational or lactation measures (assessed as described for TiO 2 ) [10,73,94,95].…”