Clinical Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2005; 11(28): 4382-4389
Published online Jul 28, 2005. doi: 10.3748/wjg.v11.i28.4382
Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis
Hiroaki Yokomori, Masaya Oda, Mariko Ogi, Go Wakabayashi, Shigeyuki Kawachi, Kazunori Yoshimura, Toshihiro Nagai, Masaki Kitajima, Masahiko Nomura, Toshifumi Hibi
Hiroaki Yokomori, Department of Internal Medicine, Kitasato Institute Medical Center Hospital, Saitama 364-8501, Japan
Masaya Oda, Organized Center of Clinical Medicine, International University of Health and Welfare, Tokyo 107-0052, Japan
Mariko Ogi, Laboratory of Pathology, Kitasato Institute Medical Center Hospital, Saitama 364-8501, Japan
Go Wakabayashi, Shigeyuki Kawachi, Masaki Kitajima, Department of Surgery, School of Medicine, Keio University, Tokyo 160-0016, Japan
Kazunori Yoshimura, Masahiko Nomura, Physiology, Saitama Medical School, Saitama 350-0495, Japan
Toshihiro Nagai, Electron Microscopy Laboratory, School of Medicine, Keio University, Tokyo 160-0016, Japan
Toshifumi Hibi, Department of Internal Medicine, School of Medicine, Keio University, Tokyo 160-0016, Japan
Author contributions: All authors contributed equally to the work.
Correspondence to: Hiroaki Yokomori, MD, Kitasato Institute Medical Center Hospital, 121-1 Arai, Kitamotoshi, Saitama 364-8501, Japan. yokomori-hr@kitasato.or.jp
Telephone: +81-485-93-1212 Fax: +81-485-93-1239
Received: July 28, 2004
Revised: August 23, 2004
Accepted: August 31, 2004
Published online: July 28, 2005
Abstract

AIM: 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, immunohi-stochemistry 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 situhybridization 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.

CONCLUSION: 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.

Keywords: Primary biliary cirrhosis, Canal of Hering, Small bile ductile, ICAM-1, LFA-1, Immunohistochemistry, Western blot, Immunogold electron microscopy