Adherence, internalization, and persistence of Helicobacter pylori in hepatocytes.
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 x 10(7) 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 beta1-integrin receptors, genistein, and cytochalasin D (P < 0.05) consistent with beta1-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. beta1-integrin is likely a receptor involved in internalization of H. pylori into hepatocytes.
Ito
Kyoko
K
Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd. 3A-320, Houston, TX 77030, USA.
Yamaoka
Yoshio
Y
Ota
Hiroyoshi
H
El-Zimaity
Hala
H
Graham
David Y
DY
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000382:microbiology / Q000473:pathology; D045744:Cell Line, Tumor; D015638:Cytochalasin D; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D019833:Genistein; D005839:Gentamicins / Q000494:pharmacology; D016481:Helicobacter Infections / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity* / Q000648:ultrastructure; D022781:Hepatocytes / Q000382:microbiology* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D008113:Liver Neoplasms / Q000382:microbiology / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D019384:Nucleic Acid Synthesis Inhibitors; D047428:Protein Kinase Inhibitors
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D019012:Integrin beta1; D019384:Nucleic Acid Synthesis Inhibitors; D047428:Protein Kinase Inhibitors; D015638:Cytochalasin D; D019833:Genistein