Modulation of bronchial epithelial cell barrier function by in vitro jet propulsion fuel 8 exposure.
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.
Robledo
R F
RF
Department of Pharmacology and Toxicology, The University of Arizona, Tucson 85724-5073, USA.
Barber
D S
DS
Witten
M L
ML
D000473:Alkanes / Q000633:toxicity; D015824:Blood-Air Barrier / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D006801:Humans; D006838:Hydrocarbons / Q000633:toxicity*; D007648:Kerosene / Q000633:toxicity*; D008353:Mannitol; D016284:Technetium Tc 99m Pentetate / Q000378:metabolism
D000473:Alkanes; D005562:Formazans; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D007648:Kerosene; C024713:n-tetradecane; D008353:Mannitol; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan; D016284:Technetium Tc 99m Pentetate