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Immunohistochemical analysis of cell–matrix adhesion molecules and their ligands in the portal tracts of primary biliary cirrhosis
Author(s) -
Yasoshima Mitsue,
Tsuneyama Koichi,
Harada Kenichi,
Sasaki Motoko,
Gershwin M. Eric,
Nakanuma Yasuni
Publication year - 2000
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(200001)190:1<93::aid-path507>3.0.co;2-a
Subject(s) - laminin , fibronectin , primary biliary cirrhosis , basement membrane , pathology , integrin , cell adhesion molecule , extracellular matrix , bile duct , biliary cirrhosis , biology , type iv collagen , immunology , medicine , microbiology and biotechnology , cell , biochemistry , autoimmune disease , disease
Intraepithelial migration of lymphoid cells (epitheliotropism) through the basement membrane of the bile duct is a key event in the development of chronic non‐suppurative destructive cholangitis (CNSDC) and eventual immune‐mediated bile duct loss in primary biliary cirrhosis (PBC). Cell‐to‐cell and cell‐to‐extracellular matrix proteins may play an important role in the development of CNSDC. To address the events of epitheliotropism in CNSDC, the expression of cell–matrix adhesion molecules such as integrins α1, α3, α4, α5, and α6 and the distribution of fibronectin, laminin, and collagen type IV were studied immunohistochemically, with emphasis on both infiltrating lymphocytes and the bile ducts, in frozen sections from 15 PBC cases and 34 controls (chronic viral hepatitis, extrahepatic biliary obstruction, and normal liver). In PBC and chronic viral hepatitis, most of the infiltrating lymphoid cells expressed integrin α4, while such expression was less common in extrahepatic biliary obstruction and normal liver. A biliary basement membrane‐like structure was delineated by immunostaining of collagen type IV and laminin in PBC and controls. On the basement membrane of CNSDC, fibronectin, a ligand of integrin α4, was strongly and frequently expressed in PBC, while such expression on the biliary basement membrane was rare in other controls. These results suggest that increased fibronectin expression on the biliary basement membrane and integrin α4–fibronectin interaction facilitate adhesion and the penetration of infiltrating α4‐expressing lymphocytes into the biliary epithelial layer in PBC. Copyright © 2000 John Wiley & Sons, Ltd.