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Modulation of bronchial epithelial cell barrier function by in vitro jet propulsion fuel 8 exposure.

Abstract
The loss of epithelial barrier integrity in bronchial and bronchiolar airways may be an initiating factor in the observed onset of toxicant-induced lung injuries. Acute 1-h inhalation exposures to aerosolized jet propulsion fuel 8 (JP-8) have been shown to induce cellular and morphological indications of pulmonary toxicity that was associated with increased respiratory permeability to 99mTc-DTPA. To address the hypothesis that JP-8 jet fuel-induced lung injury is initiated through a disruption in the airway epithelial barrier function, paracellular mannitol flux of BEAS-2B human bronchial epithelial cells was measured. Incubation of confluent cell cultures with non-cytotoxic concentrations of JP-8 or n-tetradecane (C14), a primary constituent of JP-8, for a 1-h exposure period resulted in dose-dependent increases of paracellular flux. Following exposures of 0.17, 0.33, 0.50, or 0.67 mg/ml, mannitol flux increased above vehicle controls by 10, 14, 29, and 52%, respectively, during a 2-h incubation period immediately after each JP-8 exposure. C14 caused greater mannitol flux increases of 37, 42, 63, and 78%, respectively, following identical exposure conditions. The effect on transepithelial mannitol flux reached a maximum at 12 h and spontaneously reversed to control values over a 48-h recovery period, for both JP-8 and C14 exposure. These data indicate that non-cytotoxic exposures to JP-8 or C14 exert a noxious effect on bronchial epithelial barrier function that may preclude pathological lung injury.
AuthorsR F Robledo, D S Barber, M L Witten
JournalToxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 51 Issue 1 Pg. 119-25 (Sep 1999) ISSN: 1096-6080 [Print] United States
PMID10496683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Alkanes
  • Formazans
  • Hydrocarbons
  • JP8 aviation fuel
  • Kerosene
  • n-tetradecane
  • Mannitol
  • 1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan
  • Technetium Tc 99m Pentetate
Topics
  • Alkanes (toxicity)
  • Blood-Air Barrier (drug effects)
  • Bronchi (cytology, drug effects)
  • Cell Line, Transformed
  • Dose-Response Relationship, Drug
  • Epithelial Cells (drug effects, metabolism)
  • Formazans (metabolism)
  • Humans
  • Hydrocarbons (toxicity)
  • Kerosene (toxicity)
  • Mannitol
  • Technetium Tc 99m Pentetate (metabolism)

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