AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 284-L293, Copyright © 1995 by American Physiological Society
Oxidants affect permeability and repair of the cultured human tracheal epithelium
M. Yamaya, K. Sekizawa, T. Masuda, M. Morikawa, T. Sawai and H. Sasaki
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
To examine the effects of oxidants on the airway epithelial barrier
functions, human tracheal epithelial cells were cultured on porous filter
membrane. Glucose oxidase (GO; 10 U/ml), hydrogen peroxide (H2O2; 4 x
10(-3) M), and xanthine (5 x 10(-4) M) plus xanthine oxidase (20 mU/ml)
(X-XO) significantly increased electrical conductance across epithelial
membrane (G), short-circuit current (Isc) measured with Ussing's chamber
methods, and [3H]mannitol flux through the cultured epithelium. Increases
in G and Isc induced by oxidants were significantly inhibited by catalase
(1,000 U/ml) and the protein kinase C inhibitor staurosporine (10(-7) M),
but superoxide dismutase (SOD; 100 U/ml) was without effect. GO, H2O2, and
X-XO inhibited the epithelial cell growth, [3H]thymidine incorporation by
the cells, and epithelial repair of artificially produced focal epithelial
defects (1-2 mm diam) on plastic vessels. Catalase also inhibited effects
induced by oxidants on cell growth and proliferation. These results suggest
that oxidants reduce tracheal epithelial barrier functions by damaging
tight junctions and inhibiting cell proliferation, and these effects of
oxidants on epithelial cells may be mediated by H2O2 rather than superoxide
anion and by activation of protein kinase C.
