title: In situ expression of Granzyme B and Fas-ligand in the liver of viral hepatitis.
abstract: OBJECTIVE
  The molecular mechanism involved in hepatocellular injury in viral hepatitis remains to be clarified.
  
  
  METHODS
  We investigated the in situ expression of effector molecules of cytotoxic T lymphocytes such as Fas-ligand (Fas-L), perforin and Granzyme B (Gr-B) immunohistochemically in liver tissues from 20 patients with chronic hepatitis B (CHB) and C (CHC). The degree of cell infiltration was analysed semi-quantitatively and compared with the histological activity index (HAI). Fas-L was expressed in both CD4 and CD8 T-cells in the portal tract as well as in the parenchyma.
  
  
  RESULTS
  Immunostaining of serial sections demonstrated that mononuclear cells at interface hepatitis and focal necrosis were mainly Fas-L positive CD8 T-cells. On the other hand, the expression of perforin or Gr-B was limited to a few mononuclear cells in the portal tract and parenchyma. Semi-quantitative analysis showed a positive correlation between HAI and the grade of infiltration of CD8 T-cells or Fas-L-positive cells, while the correlation was not apparent between HAI and the number of Gr-B positive cells. The expression of these molecules was not different between types of viruses.
  
  
  CONCLUSIONS
  These results suggest that Fas-L-positive CD8 T-cells play a major role in the pathogenesis of liver cell injury in chronic hepatitis.
authors.affiliation: First Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Ibuki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yabushita
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Okano
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Okamoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimada
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hakoda
authors.forename: Motowo
authors.initials: M
authors.lastname: Mizuno
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Higashi
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D053222:Fas Ligand Protein; D005260:Female; D053804:Granzymes; D019694:Hepatitis B, Chronic / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases