Pulmonary and Atherogenic Effects of Multi-Walled Carbon Nanotubes (MWCNT) in Apolipoprotein-E-Deficient Mice

Abstract

Rapid growth in nanotechnology has raised concerns regarding adverse health effects due to human exposure to manufactured nanoparticles. Carbon nanotubes (CNT) are among the most extensively used nanoparticles. This study examined pulmonary and atherosclerotic effects of multiwalled CNT (MWCNT) in a mouse model of atherosclerosis. Female apolipoprotein E-deficient (apoE–/–) mice were exposed to 40 μg MWCNT, once each week for 16 consecutive weeks by pharyngeal aspiration. On d 1 after the last administration, tissues were extracted from half the group, while the remaining animals were sacrificed at d 7. Bronchoalveolar lavage (BAL) was performed to obtain BAL fluid. In addition, plasma, lung, and aortas were extracted to assess pulmonary inflammation and atherosclerotic lesion formation. Polymorphonuclear leukocytes and total BAL cell number increased significantly in MWCNT-exposed mice on d 1 and 7 postexposure. Cell-free BAL fluid obtained from MWCNT-exposed mice at d 1 and 7 postexposure contained significantly elevated levels of total protein, lactate dehydrogenase (LDH), surfactant protein-D, and mucin. Although MWCNT exposure increased pulmonary injury and inflammation, the aortic intimal surface covered by atherosclerotic lesions was not significantly different between control apoE–/– mice and apoE–/– MNCNT-treated animals. Total plasma cholesterol concentrations also were not markedly affected by MWCNT exposure. These results demonstrate that pulmonary exposure to MWCNT affects local airway inflammation but did not appear to augment progression of atherosclerosis in female apoE–/– mice.