Helicobacter pylori Toxin Affects Epithelia Permeability

The effects of the vacuolating toxin (VacA) released by pathogenic strains of Helicobacter pylori on several polarized epithelial monolayers were investigated. Trans-epithelial electric resistance (TER) of monolayers formed by canine kidney MDCK I, human gut T84, and murine mammary gland epH4, was lowered by acid-activated VacA. Independent of the cell type and of the starting TER value, VacA reduced it to a minimal value of 1,000–1,300 V 3 cm 2 . TER decrease was paralleled by a threeto fourfold increase of [ 14 C]-mannitol (molecular weight 182.2) and a twofold increase of [ 14 C]-sucrose (molecular weight 342.3) transmonolayer flux. On the contrary, transmembrane flux of the proinflammatory model tripeptide [ 14 C]N -formylMet-Leu-Phe (molecular weight 437.6), of [ 3 H]-inuline (molecular weight 5,000) and of HRP (molecular weight 47,000) did not change. These data indicate that VacA increases paracellular epithelial permeability to molecules with molecular weight , 350–440. Accordingly, the epithelial permeability of Fe 3 1 and Ni 2 1 ions, essential for H. pylori survival in vivo, was also increased by VacA. High-resolution immunofluorescence and SDS-PAGE analysis failed to reveal alterations of junctional proteins ZO-1, occludin, cingulin, and E-cadherin. It is proposed that induction by VacA of a selective permeabilization of the epithelial paracellular route to low molecular weight molecules and ions may serve to supply nutrients, which favor H. pylori growth in vivo . ( J. Clin. Invest. 1998. 102:813–820.)