Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

• Published in: PloS one 2017-04, Vol.12 (4), p.e0174167-e0174167
• Main Authors: Poulsen, Sarah S, Knudsen, Kristina B, Jackson, Petra, Weydahl, Ingrid E K, Saber, Anne T, Wallin, Håkan, Vogel, Ulla
• Format: Article
• Language: English
• Subjects: Acute phase proteins; Acute phase substances; Acute-Phase Proteins - metabolism; Acute-Phase Reaction - metabolism; Analysis; Animal models; Animals; Apolipoprotein E; Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Biophysics; Blood proteins; C-reactive protein; Carbon; Cardiovascular disease; Cardiovascular diseases; Chemical Phenomena - drug effects; Cholesterol; Chronic obstructive pulmonary disease; Cobalt; Cytotoxicity; Engineering and Technology; Exposure; Female; Gallium arsenide; Gene expression; Granuloma; Health risks; Inflammation; Inhalation; Inhalation Exposure - adverse effects; Interleukin 6; Isoforms; Lung - drug effects; Lung - metabolism; Lung diseases; Mammary gland; Medicine and Health Sciences; Metals; Mice; Mice, Inbred C57BL; Movement disorders; Multi wall carbon nanotubes; Multiple regression analysis; Nanomaterials; Nanotechnology; Nanotubes; Nanotubes, Carbon - adverse effects; Neurodegenerative diseases; Neutrophils - metabolism; Oxidation; Oxidative stress; Parkinson's disease; Physical Sciences; Physicochemical properties; Physiological aspects; Plague; Plasma; Proteins; Research and Analysis Methods; Risk factors; RNA, Messenger - metabolism; Rodents; Serum Amyloid A Protein - metabolism; Studies; Toxicity; Vasodilation; β-Amyloid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174167

Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) has been linked to an increased risk of developing cardiovascular disease in addition to the well-documented physicochemical-dependent adverse lung effects. A proposed mechanism is through a strong and sustained pulmonary secretion of acute phase proteins to the blood. We identified physicochemical determinants of MWCNT-induced systemic acute phase response by analyzing effects of pulmonary exposure to 14 commercial, well-characterized MWCNTs in female C57BL/6J mice pulmonary exposed to 0, 6, 18 or 54 μg MWCNT/mouse. Plasma levels of acute phase response proteins serum amyloid A1/2 (SAA1/2) and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saa1 and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater and lasted longer than hepatic Saa1 mRNA expression. Plasma SAA1/2 and SAA3 protein levels were related to time and physicochemical properties using adjusted, multiple regression analyses. SAA3 and SAA1/2 plasma protein levels were increased after exposure to almost all of the MWCNTs on day 1, whereas limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length resulted in lowered SAA1/2 plasma levels. Increased SAA3 protein levels were positively related to dose and content of Mn, Mg and Co on day 1, whereas oxidation and diameter of the MWCNTs were protective on day 28 and 92, respectively. The results of this study reveal very differently controlled pulmonary and hepatic acute phase responses after MWCNT exposure. As the responses were influenced by the physicochemical properties of the MWCNTs, this study provides the first step towards designing MWCNT that induce less SAA.