Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 protein and messenger RNA in primary biliary cirrhosis.
OBJECTIVE
This study examined the role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in the autoimmune process of bile duct destruction in the early stages of primary biliary cirrhosis (PBC).


METHODS
Ten PBC liver samples and five control samples were studied. Immunohistochemical studies of ICAM-1 and LFA-1, and Western blot of ICAM-1 were performed. Immunoelectron microscopy was conducted using immunoglobulin-gold and silver staining. Human ICAM-land LFA-1 peptide nucleic acid probes were used for in situ hybridization.


RESULTS
In PBC liver samples, immunohistochemistry showed aberrant ICAM-1 expression on bile duct epithelial plasma membrane and also luminal sites of endothelial plasma membrane of terminal portal venules. Western blot confirmed ICAM-1 protein expression. LFA-1-positive lymphocytes were associated with epithelial cells of septal and interlobular bile ducts. Immunoelectron microscopy localized ICAM-1 on the luminal and basal surfaces as well as on lymphocytes around damaged bile duct epithelial cells, and LFA-1 on lymphocytes around damaged bile ducts. Messenger RNA expression of ICAM-1 was demonstrated in bile ducts, and LFA-1 in lymphocytes around bile ducts.


CONCLUSIONS
De novo expression of ICAM-1 and LFA-1 at protein and mRNA levels in PBC may imply an inductive role of ICAM-1 through binding with its ligand LFA-1 in the extravasation of activated lymphocytes and lymphocyte-mediated bile duct destruction.
Yokomori
Hiroaki
H
Department of Internal Medicine, Kitasato Institute Medical Center Hospital, Kitamotoshi, Saitama.
Oda
Masaya
M
Yoshimura
Kazunori
K
Nomura
Masahiko
M
Ogi
Mariko
M
Wakabayashi
Go
G
Kitajima
Masaki
M
Ishii
Hiromasa
H
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000276:immunology
D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1