The cultured human cervical epithelium: a new model for studying paracellular transport

Abstract

Objective: Human cervical cells form confluent cultures on filters with a relatively high degree of paracellular permeability. We sought to determine the extent to which acute and reversible changes in permeability in responses to modulators of paracellular resistance affect the resistance of the lateral intercellular space (RLIS), or of the tight junctions (RTJ).

Methods: The question was approached experimentally by measuring the effects of combinations of physical/chemical conditions whose actions on the paracellular resistance are relatively well understood (e.g., changes in hydrostatic gradients, medium tonicity, and medium calcium concentration). Changes in paracellular permeability were determined relative to changes in transepithelial electrical resistance (TER) and to the epithelial permeability to the trisulfonic acid pyranine (Ppyr). Changes in RTJ were determined relative to changes in the transepithelial cation selectivity, as determined from changes in dilution potential.

Results: 1) Low extracellular calcium abrogates the TER and decrease transepithelial cation selectivity (i.e., decreases RTJ). 2) Changes in TER induced by changes in hydrostatic gradients and medium tonicity modulate TER but have no effect on cation selectivity (i.e., the effect was on RLIS). 3) Low-calcium-related decreases in TER are additive to those of hydrostatic and hypertonic gradients and hypotonic conditions. 4) Subluminal to luminal hydrostatic and hypertonic gradients decrease TER, but the effects are nonadditive.

Conclusions: These results indicate that RLIS and RTJ can be selectively modulated. Based on quantitative analysis of the data it is predicated that RLIS and RTJ constitute the TER of the cultured cervical epithelium, and contribute about 25 and 75%, respectively, to the total resistance.