Evidence of angiogenesis in primary biliary cirrhosis: an immunohistochemical descriptive study.
OBJECTIVE
The intrahepatic inflammatory process occurring during primary biliary cirrhosis contributes to bile duct destruction, but the cellular and molecular pathways involved are largely unknown. Furthermore, additional pathogenetic mechanisms may exist. We aimed at evaluating the cellular infiltrate phenotype; the expression of lymphocyte activation, antigen recognition and cell-adhesion molecules; the occurrence of hepatic angiogenesis and the molecules involved.


METHODS
Immunohistochemical investigations were performed in frozen liver biopsy sections from primary biliary cirrhosis patients.


RESULTS
CD8+ and CD69+ T cells were predominant in inflammatory infiltrates around damaged cholangiocytes; beta2-microglobulin conformational epitope and intercellular adhesion molecule-1 expression were enhanced in bile ducts and hepatocytes. Inflamed portal areas showed vascular cell adhesion molecule-1 up-regulation; formation of tubule-like structures (neovessels) by endothelial cells expressing vascular endothelial-cadherin and CD-31; vascular endothelial growth factor expression in surrounding sinusoidal endothelial cells; and enhanced expression of angiopoietins 1 and 2, their receptor Tie-2 and endoglin, suggesting their involvement in new vascular structure formation.


CONCLUSIONS
The inflammatory infiltrate in primary biliary cirrhosis shows an increased reactivity for lymphocyte activation, antigen recognition and cell- and vascular-adhesion molecules. Additionally, intrahepatic angiogenesis occurs, involving vascular endothelial growth factor, angiopoietins 1 and 2, Tie-2 and endoglin in neovessel formation.
Medina
Jesús
J
Unidad de Hepatología (planta 3), Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Diego de León 62, E-28006 Madrid, Spain.
Sanz-Cameno
Paloma
P
García-Buey
Luisa
L
Martín-Vílchez
Samuel
S
López-Cabrera
Manuel
M
Moreno-Otero
Ricardo
R
D000328:Adult; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008105:Liver Cirrhosis, Biliary / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1