Extracellular pH modulates Helicobacter pylori-induced vacuolation and VacA toxin internalization in human gastric epithelial cells

Vittorio Ricci, Patrizia Sommi, Roberto Fiocca, Vittorio Necchi, Marco Romano, Enrico Solcia

Research output: Contribution to journalArticlepeer-review

Abstract

In this study we investigated whether an acidic extracellular pH may inhibit H. pylori-induced internalization of bacterial virulence factors by gastric epithelium, thus preventing ingestion of potentially dangerous luminal contents and resulting cellular damage. The interaction of H. pylori VacA toxin and ammonia (produced by H. pylori urease) with partly polarized gastric MKN 28 cells in culture was investigated at neutral and moderately acidic pH (6.2, compatible with cell viability) by means of neutral red dye uptake and ultrastructural immunocytochemistry. We found that acidic extracellular pH virtually abolished both VacA-dependent and ammonia-dependent cell vacuolation, as shown by the neutral red test, and caused a 50% decrease in VacA internalization into endosomal vesicles and vacuoles, as assessed by quantitation of immunogold particles. In addition, acidic pH blocked endosomal internalization of H. pylori outer membrane vesicles, a convenient indicator of endocytosis. Our data raise the possibility that suppression of gastric acid may increase H. pylori-induced gastric damage by enhancing epithelial internalization of H. pylori virulence factors through activation of endocytosis. Increased transmembrane diffusion of ammonia could also contribute to this process.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume292
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • Cell vacuolation
  • Extracellular pH
  • Helicobacter pylori
  • Ultrastructural immunocytochemistry
  • VacA internalization

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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