POLYCATION-INDUCED ENHANCEMENT OF EPITHELIAL PARACELLULAR PERMEABILITY IS INDEPENDENT OF TIGHT JUNCTIONAL CHARACTERISTICS

The nature of polycation-induced change in transepithelial permeabilit y was investigated in strains I (tight) and II (leaky) MDCK epithelial monolayers. Apical exposure to poly(L-lysine) (PLL, mol. wt. (MW) alm ost-equal-to 20000) induced a dose-dependent increase in transepitheli al conductance (G(T)) in both strains which correlated with increasing transepithelial flux of extracellular markers (thiourea/inulin) indic ating that PLL enhanced paracellular permeability in these epithelia. Coincident with the increase in G(T), PLL also induced an inward short circuit current (I(sc)) which was associated with the early phase of the increase in G(T) and may be responsible for part of it. Morphologi cal studies showed that immunofluorescent staining of the tight juncti on protein, ZO-1, was abolished following PLL exposure. In addition, F -actin staining in monolayers challenged with PLL demonstrated breaks in the zonulae occludentes at the apical surface. PLL had similar effe cts on monolayers of T84 and HCT-8 human intestinal cells indicating t hat polycation action may be general for a range of epithelial types. We conclude that epithelial exposure to polycations results in opening of the paracellular route by mechanisms which are independent of tigh t junction characteristics.