Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat

J Clin Invest. 1998 Jul 15;102(2):445-54. doi: 10.1172/JCI3169.


To determine whether asbestos inhalation induces the formation of reactive nitrogen species, three groups of rats were exposed intermittently over 2 wk to either filtered room air (sham-exposed) or to chrysotile or crocidolite asbestos fibers. The rats were killed at 1 or 6 wk after exposure. At 1 wk, significantly greater numbers of alveolar and pleural macrophages from asbestos-exposed rats than from sham-exposed rats demonstrated inducible nitric oxide synthase protein immunoreactivity. Alveolar macrophages from asbestos-exposed rats also generated significantly greater nitrite formation than did macrophages from sham-exposed rats. Strong immunoreactivity for nitrotyrosine, a marker of peroxynitrite formation, was evident in lungs from chrysotile- and crocidolite-exposed rats at 1 and 6 wk. Staining was most evident at alveolar duct bifurcations and within bronchiolar epithelium, alveolar macrophages, and the visceral and parietal pleural mesothelium. Lungs from sham-exposed rats demonstrated minimal immunoreactivity for nitrotyrosine. Significantly greater quantities of nitrotyrosine were detected by ELISA in lung extracts from asbestos-exposed rats than from sham-exposed rats. These findings suggest that asbestos inhalation can induce inducible nitric oxide synthase activation and peroxynitrite formation in vivo, and provide evidence of a possible alternative mechanism of asbestos-induced injury to that thought to be induced by Fenton reactions.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Asbestos, Crocidolite / toxicity*
  • Asbestos, Serpentine / toxicity*
  • Bronchoalveolar Lavage
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Inhalation Exposure*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / metabolism
  • Male
  • Nitrates / metabolism*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type II
  • Nitrogen Dioxide / metabolism
  • Pleura
  • Pleural Effusion
  • Rats
  • Rats, Inbred F344
  • Reactive Oxygen Species / metabolism*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism*


  • Asbestos, Serpentine
  • Nitrates
  • Reactive Oxygen Species
  • Asbestos, Crocidolite
  • peroxynitric acid
  • Tyrosine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Nitrogen Dioxide