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ToxSci Advance Access published online on July 28, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm196
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pulmonary and Systemic Immune Response to Inhaled Multiwalled Carbon Nanotubes

Leah A. Mitchell*,{ddagger}, Jun Gao*, Randy Vander Wal{dagger}, Andrew Gigliotti{ddagger}, Scott W. Burchiel* and Jacob D. McDonald{ddagger},§

* College of Pharmacy, University of New Mexico, Albuquerque, NM 87131-0001 {dagger} The National Center for Microgravity Research (NCMR), c/o The NASA-Glenn Research Center, Cleveland, OH 44135 {ddagger} Lovelace Respiratory Research Institute, Albuquerque, NM 87108

§ Corresponding Author: Jacob D. McDonald, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, Phone: 505-348-9455, Fax: 505-348-4980, jmcdonal{at}lrri.org

Received May 27, 2007; revision received July 17, 2007; accepted July 18, 2007


  Abstract

Inhalation of multiwalled carbon nanotubes (MWCNTs) at particle concentrations ranging from 0.3–5 mg/m3 did not result in significant lung inflammation or tissue damage, but caused systemic immune function alterations. C57BL/6 adult (10-12 week) male mice were exposed by whole-body inhalation to control air or 0.3, 1, or 5 mg/m3 respirable aggregates of MWCNTs for 7 or 14 days (6 h/day). Histopathology of lungs from exposed animals showed alveolar macrophages containing black particles; however, there was no inflammation or tissue damage observed. Bronchial alveolar lavage fluid also demonstrated particle-laden macrophages; however, white blood cell counts were not increased compared to controls. MWCNT exposures to 0.3 mg/m3 and higher particle concentrations caused non-monotonic systemic immunosuppression after 14 days but not after 7 days. Immunosuppression was characterized by reduced T-cell-dependent antibody response to sheep erythrocytes as well as T-cell proliferative ability in presence of mitogen, Concanavalin A (Con A). Assessment of nonspecific natural killer (NK) cell activity showed that animals exposed to 1 mg/m3 had decreased NK cell function. Gene expression analysis of selected cytokines and an indicator of oxidative stress were assessed in lung tissue and spleen. No changes in gene expression were observed in lung; however, interleukin 10 (IL-10) and NAD(P)H oxidoreductase 1 (NQO1) mRNA levels were increased in spleen.

Key Words: Carbon nanotubes; inhalation; pulmonary pathology; immunosuppression.

Author e-mail addresses: lmitchell{at}lrri.org, jgao{at}salud.unm.edu, randyvanderwal{at}grc.nasa.gov, agigliot{at}lrri.org, sburchiel{at}sauld.unm.edu


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