Polycation-induced enhancement of epithelial paracellular permeability is independent of tight junctional characteristics

Abstract

The nature of polycation-induced change in transepithelial permeability was investigated in strains I ( tight) and II ( leaky) MDCK epithelial monolayers. Apical exposure to poly( l-lysine) ( PLL, mol. wt. ( MW) ≈ 20 000) induced a dose-dependent increase in transepithelial conductance (G T ) in both strains which correlated with increasing transepithelial flux of extracellular markers (thiourea/inulin) indicating 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. Morphological studies showed that immunofluorescent staining of the tight junction 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 effects on monolayers of T 84 and HCT-8 human intestinal cells indicating that 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 tight junction characteristics.