NO2 decreases paracellular resistance to ion and solute flow in alveolar epithelial monolayers.
Primary cultured monolayers of rat alveolar epithelial cells grown on tissue culture-treated Nuclepore filters were exposed to 2.5 ppm nitrogen dioxide (NO2) for 2-20 min. Changes in monolayer bioelectric properties and solute permeabilities were subsequently measured. Exposure to NO2 produced a dose-dependent decrease in monolayer transepithelial electrical resistance (Rt), whereas monolayer short-circuit current was unaffected. Post-exposure monolayer permeability to 14C-sucrose (which primarily crosses alveolar epithelium via the paracellular pathway) increased markedly. That for 3H-glycerol (which permeates through both paracellular and transcellular pathways) increased to a lesser extent. Partial recovery of Rt and solute permeabilities was noted by 48-h post-exposure. The time courses of the decrease in Rt and increase in solute permeabilities were similar. These results suggest that NO2 primarily impairs passive alveolar epithelial barrier functions in vitro, probably by altering intercellular junctions, and does not appear to directly affect cell membrane active ion transport processes. When correlated with results obtained from experimental approaches, studies of in vitro alveolar epithelial monolayers may facilitate investigations of dosimetry, sites, and mechanisms of oxidant injury in the lung.
Cheek
J M
JM
Seaver Cardiopulmonary Laboratory, Will Rogers Institute Pulmonary Research Program, Cornell University Medical College, New York, New York.
Kim
K J
KJ
Crandall
E D
ED
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005990:Glycerol / Q000493:pharmacokinetics; D007477:Ions; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009585:Nitrogen Dioxide / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000493:pharmacokinetics
D000393:Air Pollutants; D007477:Ions; D013395:Sucrose; D005990:Glycerol; D009585:Nitrogen Dioxide