title: Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis.
abstract: OBJECTIVE
  To examine the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) expression on canals of Hering (CoH) and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis (PBC).
  
  
  METHODS
  Ten wedged liver biopsies of PBC (five cases each of stages 2 and 3) were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse mAbs. In situ hybridization was done to examine the messenger RNA expression of ICAM-1 in formalin-fixed, paraffin-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification (CSA) technique. Immunogold-silver staining for electron microscopy was performed using anti-ICAM and anti-LFA-1 mouse mAbs. The immunogold particles on epithelial cells of bile ductules and cholangiocytes of CoH cells were counted and analyzed semi-quantitatively. Western blotting was performed to confirm ICAM-1 protein expression.
  
  
  RESULTS
  In liver tissues of PBC patients, immunohistochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules, and also on mature cholangiocytes but not on hepatocytes in CoH. LFA-1-positive lymphocytes were closely associated with epithelial cells in bile ductules. ICAM-1 expression at protein level was confirmed by Western blot. In situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the bile ductules. By immunoelectron microscopy, ICAM-1 was demonstrated on the basal surface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged CoH. Cells with intermediate morphology resembling progenitor cells in CoH were not labeled with ICAM-1 and LFA-1.
  
  
  CONCLUSIONS
  De novo expression of ICAM-1 both on mature cholangiocytes in CoH and epithelial cells in bile ductules in PBC implies that lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the CoH.
authors.affiliation: Kitasato Institute Medical Center Hospital, 121-1 Arai, Kitamotoshi, Saitama 364-8501, Japan. yokomori-hr@kitasato.or.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yokomori
authors.forename: Masaya
authors.initials: M
authors.lastname: Oda
authors.forename: Mariko
authors.initials: M
authors.lastname: Ogi
authors.forename: Go
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawachi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nomura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000368:Aged; D001652:Bile Ducts / Q000473:pathology / Q000502:physiology*; D001706:Biopsy; D002448:Cell Adhesion / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008875:Middle Aged
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1