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Nitrogen dioxide induces death in lung epithelial cells in a density-dependent manner.

Abstract
Nitrogen dioxide (*NO2) is commonly known as an indoor and outdoor air pollutant. Inhalation of *NO2 is associated with epithelial cell injury, inflammation, and the aggravation of asthma. *NO2 can also be formed during inflammation, by the metabolism of nitric oxide. We describe a gas-phase exposure system for in vitro exposure of lung epithelial cells to *NO2. Immunofluorescence revealed 3-nitrotyrosine immunoreactivity of rat alveolar type II epithelial cells exposed to 5 parts per million of *NO2 for 4 h. Comparative analysis of log-phase and confluent cultures demonstrated that cell death occurred extensively in log-phase cells, whereas minimal death was observed in confluent cultures. Peroxynitrite (ONOO-) or the ONOO- generator 3-morpholinosydnonimine (SIN-1) caused similar amounts of death. Further, exposure of wounded cell cultures to *NO(2) or SIN-1 revealed that death was restricted to cells repopulating a wounded area. Cycloheximide or actinomycin D, inhibitors or protein and messenger RNA synthesis, respectively, significantly reduced terminal transferase reactivity, suggesting that a new protein(s) may be required for cell death. These results suggest that during restitution after pulmonary injury, epithelium may be sensitive to cell death by reactive nitrogen species.
AuthorsR L Persinger, W M Blay, N H Heintz, D R Hemenway, Y M Janssen-Heininger
JournalAmerican journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 24 Issue 5 Pg. 583-90 (May 2001) ISSN: 1044-1549 [Print] United States
PMID11350828 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Culture Media, Conditioned
  • DNA, Single-Stranded
  • Nitrates
  • Nitric Oxide Donors
  • Nitrites
  • peroxynitric acid
  • linsidomine
  • Molsidomine
  • Nitrogen Dioxide
Topics
  • Cell Count
  • Cell Death (drug effects)
  • Cells, Cultured
  • Culture Media, Conditioned
  • DNA, Single-Stranded (metabolism)
  • In Situ Nick-End Labeling
  • Lung (cytology, drug effects, metabolism)
  • Molsidomine (analogs & derivatives, pharmacology)
  • Nitrates (metabolism, pharmacology)
  • Nitric Oxide Donors (pharmacology)
  • Nitrites (metabolism)
  • Nitrogen Dioxide (pharmacology)
  • Oxidative Stress (drug effects)
  • Respiratory Mucosa (cytology, drug effects, metabolism)

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