OXIDANTS AFFECT PERMEABILITY AND REPAIR OF THE CULTURED HUMAN TRACHEAL EPITHELIUM

To examine the effects of oxidants on the airway epithelial barrier fu nctions, human tracheal epithelial cells were cultured on porous filte r 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 epith elial membrane (G), short-circuit current (I-sc) measured with Ussing' s chamber methods, and [H-3]mannitol flux through the cultured epithel ium. Increases in G and I-sc induced by oxidants were significantly in hibited by catalase (1,000 U/ml) and the protein kinase C inhibitor st aurosporine (10(-7) M), but superoxide dismutase (SOD; 100 U/ml) was w ithout effect. GO, H2O2, and X-XO inhibited the epithelial cell growth , [H-3]thymidine incorporation by the cells, and epithelial repair of artificially produced focal epithelial defects (1-2 mm diam) on plasti c 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 epithe lial cells may be mediated by H2O2 rather than superoxide anion and by activation of protein kinase C.