TY - JOUR
T1 - Immunohistochemical analysis of cell-matrix adhesion molecules and their ligands in the portal tracts of primary biliary cirrhosis
AU - Yasoshima, Mitsue
AU - Tsuneyama, Koichi
AU - Harada, Kenichi
AU - Sasaki, Motoko
AU - Gershwin, M. Eric
AU - Nakanuma, Yasuni
PY - 2000/1
Y1 - 2000/1
N2 - 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.
AB - 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.
KW - Biliary tree
KW - Epitheliotropism
KW - Fibronectin
KW - Integrin
KW - Primary biliary cirrhosis
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U2 - 10.1002/(SICI)1096-9896(200001)190:1<93::AID-PATH507>3.0.CO;2-A
DO - 10.1002/(SICI)1096-9896(200001)190:1<93::AID-PATH507>3.0.CO;2-A
M3 - Article
C2 - 10640998
AN - SCOPUS:0033955026
VL - 190
SP - 93
EP - 99
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 1
ER -