Another Pathway to Non-cancer Nanoparticle Toxicity

American Journal of Respiratory Cell and Molecular Biology. Vol. 40, pp. 349-358, 2009© 2009 American Thoracic Society

Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma

Jessica P. Ryman-Rasmussen1,2, Earl W. Tewksbury2, Owen R. Moss2, Mark F. Cesta1,2,3, Brian A. Wong2 and James C. Bonner1,2
1 Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina; 2 The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina; and 3 Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina
Correspondence and requests for reprints should be addressed to James C. Bonner, Ph.D., North Carolina State University, Box 7633, Raleigh, NC 27695. E-mail: james_bonner@ncsu.edu
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Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m3) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-β1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-β1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-β1, which stimulates collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.
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BrooklynDodger(s) Comment: This study provides another view of the toxic potential of carbon nanotubes. The small numbers of mice and short exposure time means these data don't support inference of a threshold or no risk without allergic inflammation. The data do support an inference that persons with allergic inflammation might be less resistent to nano particles.