Digestive Diseases and Sciences

, Volume 53, Issue 9, pp 2541–2549 | Cite as

Adherence, Internalization, and Persistence of Helicobacter pylori in Hepatocytes

  • Kyoko Ito
  • Yoshio Yamaoka
  • Hiroyoshi Ota
  • Hala El-Zimaity
  • David Y. Graham
Original Paper
First Online:
Received:
Accepted:

Abstract

Although Helicobacter pylori have been identified in the liver, the role of Helicobacter sp. in human liver diseases remains unclear. This study explored whether H. pylori were internalized and could persist in hepatocytes. The majority of an inoculum of H. pylori (1 × 107 colony forming units) adhered to hepatocytes. Using the gentamicin invasion assay we found that approximately 2% were internalized and persisted following passage for more than 2 months. Electron microscopy confirmed the presence of intracellular Helicobacter. The number of adherent or internalized H. pylori was significantly greater with hepatocytes than with gastric epithelial cells (P < 0.05) and was also dependent on cag pathogenicity island (PAI), VacA, OipA, or BabA status. Transmission electron microscopy was used to confirm adherence and invasion of H. pylori into hepatocytes. Internalization of H. pylori was inhibited by antibodies to β1-integrin receptors, genistein, and cytochalasin D (P < 0.05) consistent with β1-integrin acting as a surface receptor with additional requirements for tyrosine kinase phosphorylation and actin polymerization. In summary, H. pylori both adhered to and invaded into hepatocytes in vitro, depending on the virulent factors, and persisted within hepatocytes during subcultures. β1-integrin is likely a receptor involved in internalization of H. pylori into hepatocytes.

Keywords

Helicobacter Adherence Internalization Persistence Hepatocytes 
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Notes

Acknowledgements

We are grateful to Dr. Gretchen Darlington, Dr. Borris Yoffe, Dr. Norman Sussman, and Dr. Milton Finegold for insightful discussions as assistance. Also, we thank Jian Wu and James Barrish for excellent technical assistance. This material is based upon work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338 which funds the Texas Gulf Coast Digestive Diseases Center. Dr. Yoshio Yamaoka is supported in part by NIH grant DK 62813. Dr. Kyoko Ito was supported in part by an International GI Training Grant from the American College of Gastroenterology.

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Copyright information

© US Government (Michael E. DeBakey VA Medical Center) 2008

Authors and Affiliations

  • Kyoko Ito
    • 1
    • 2
  • Yoshio Yamaoka
    • 1
  • Hiroyoshi Ota
    • 3
  • Hala El-Zimaity
    • 1
  • David Y. Graham
    • 1
  1. 1.Department of Medicine, Michael E. DeBakey VA Medical CenterBaylor College of MedicineHoustonUSA
  2. 2.Division of Gastroenterology and Hepatology, Department of Internal MedicineThe Jikei School of MedicineTokyoJapan
  3. 3.Department of Biomedical Laboratory Sciences, School of Health SciencesShinshu University, School of MedicineNaganoJapan

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