Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice

Anna A. Shvedova, Elena R. Kisin, Robert Mercer, Ashley R. Murray, Victor J. Johnson, Alla I. Potapovich, Yulia Y. Tyurina, Olga Gorelik, Sevaram Arepalli, Diane Schwegler-Berry, Ann F. Hubbs, James Antonini, Douglas E. Evans, Bon Ki Ku, Dawn Ramsey, Andrew Maynard, Valerian E. Kagan, Vincent Castranova, Paul Baron

Research output: Contribution to journalArticlepeer-review

1247 Scopus citations


Single-walled carbon nanotubes (SWCNT) are new materials of emerging technological importance. As SWCNT are introduced into the life cycle of commercial products, their effects on human health and environment should be addressed. We demonstrated that pharyngeal aspiration of SWCNT elicited unusual pulmonary effects in C57BL/6 mice that combined a robust but acute inflammation with early onset yet progressive fibrosis and granulomas. A dose-dependent increase in the protein, LDH, and γ-glutamyl transferase activities in bronchoalveolar lavage were found along with accumulation of 4-hydroxynonenal (oxidative biomarker) and depletion of glutathione in lungs. An early neutrophils accumulation (day 1), followed by lymphocyte (day 3) and macrophage (day 7) influx, was accompanied by early elevation of proinflammatory cytokines (TNF-α, IL-1β; day 1) followed by fibrogenic transforming growth factor (TGF)-β1 (peaked on day 7). A rapid progressive fibrosis found in mice exhibited two distinct morphologies: 1) SWCNT-induced granulomas mainly associated with hypertrophied epithelial cells surrounding SWCNT aggregates and 2) diffuse interstitial fibrosis and alveolar wall thickening likely associated with dispersed SWCNT. In vitro exposure of murine RAW 264.7 macrophages to SWCNT triggered TGF-β1 production similarly to zymosan but generated less TNF-α and IL-1β. SWCNT did not cause superoxide or NO. production, active SWCNT engulfment, or apoptosis in RAW 264.7 macrophages. Functional respiratory deficiencies and decreased bacterial clearance (Listeria monocytogenes) were found in mice treated with SWCNT. Equal doses of ultrafine carbon black particles or fine crystalline silica (SiO2) did not induce granulomas or alveolar wall thickening and caused a significantly weaker pulmonary inflammation and damage.

Original languageEnglish (US)
Pages (from-to)L698-L708
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number5 33-5
StatePublished - Nov 2005
Externally publishedYes


  • Cytokines
  • Inflammation
  • Microbial infection
  • Nanoparticles

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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