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

G T McEwan, M A Jepson, B H Hirst, N L Simmons

Research output: Contribution to journalArticle

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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) approximately 20,000) induced a dose-dependent increase in transepithelial conductance (GT) 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 GT, PLL also induced an inward short circuit current (Isc) which was associated with the early phase of the increase in GT 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 T84 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.
Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalBiochimica et Biophysica Acta
Volume1148
Issue number1
Publication statusPublished - 14 May 1993

Fingerprint

Permeability
Zonula Occludens-1 Protein
Staining and Labeling
Thiourea
Inulin
Tight Junctions
Lysine
Actins
Epithelium
polycations

Keywords

  • Actins
  • Animals
  • Carbon Radioisotopes
  • Cell Line
  • Cell Membrane Permeability
  • Colon
  • Dogs
  • Electrophysiology
  • Epithelium
  • Humans
  • Intercellular Junctions
  • Intestinal Neoplasms
  • Inulin
  • Kidney
  • Polylysine
  • Thiourea
  • Tritium
  • Tumor Cells, Cultured

Cite this

Polycation-induced enhancement of epithelial paracellular permeability is independent of tight junctional characteristics. / McEwan, G T; Jepson, M A; Hirst, B H; Simmons, N L.

In: Biochimica et Biophysica Acta, Vol. 1148, No. 1, 14.05.1993, p. 51-60.

Research output: Contribution to journalArticle

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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) approximately 20,000) induced a dose-dependent increase in transepithelial conductance (GT) 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 GT, PLL also induced an inward short circuit current (Isc) which was associated with the early phase of the increase in GT 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 T84 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.",
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N2 - 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) approximately 20,000) induced a dose-dependent increase in transepithelial conductance (GT) 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 GT, PLL also induced an inward short circuit current (Isc) which was associated with the early phase of the increase in GT 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 T84 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.

AB - 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) approximately 20,000) induced a dose-dependent increase in transepithelial conductance (GT) 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 GT, PLL also induced an inward short circuit current (Isc) which was associated with the early phase of the increase in GT 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 T84 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.

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