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PMID: 9710450 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin.

The Journal of clinical investigation ·Vol. 102 ·No. 4 ·1998-08-15 ·Pages 813-20

Papini E, Satin B, Norais N, de Bernard M, Telford JL, Rappuoli R, Montecucco C

Abstract

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 Omega x cm2. TER decrease was paralleled by a three- to fourfold increase of [14C]-mannitol (molecular weight 182.2) and a twofold increase of [14C]-sucrose (molecular weight 342.3) transmonolayer flux. On the contrary, transmembrane flux of the proinflammatory model tripeptide [14C]-N-formyl-Met-Leu-Phe (molecular weight 437.6), of [3H]-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 Fe3+ and Ni2+ 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.

MeSH Terms
Animals Bacterial Proteins/pharmacology Bacterial Toxins/pharmacology Biological Transport/drug effects Caco-2 Cells Cadherins/isolation & purification Cations/metabolism Cell Polarity Dogs Dose-Response Relationship, Drug Epithelial Cells/drug effects HeLa Cells Helicobacter pylori Horseradish Peroxidase/metabolism Humans Hydrogen-Ion Concentration Intercellular Junctions/drug effects Inulin/metabolism Iron/metabolism Mannitol/metabolism Membrane Proteins/isolation & purification N-Formylmethionine Leucyl-Phenylalanine/metabolism Nickel/metabolism Permeability/drug effects Stomach Ulcer/etiology Sucrose/metabolism
Chemicals
Bacterial Proteins Bacterial Toxins Cadherins Cations Membrane Proteins VacA protein, Helicobacter pylori Mannitol Sucrose N-Formylmethionine Leucyl-Phenylalanine Nickel Inulin Iron Horseradish Peroxidase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Papini E
Centro CNR Biomembrane and Dipartimento di Scienze, Biomediche, Università di Padova, 35121 Padova, Italy. [email protected]
Satin B
Norais N
de Bernard M
Telford J L
Rappuoli R
Montecucco C
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI2764
Email
[email protected]
Published
1998-08-15
Pages
813-20
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508944
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI2764 PMC Full Text View journal details
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