Evidence of angiogenesis in primary biliary cirrhosis:: an immunohistochemical descriptive study

被引:80
作者
Medina, J
Sanz-Cameno, P
García-Buey, L
Martín-Vílchez, S
López-Cabrera, M
Moreno-Otero, R
机构
[1] Univ Autonoma Madrid, Hosp Univ Princesa, Unidad Hepatol Planta 3, E-28006 Madrid, Spain
[2] Univ Autonoma Madrid, Hosp Univ Princesa, Unidad Biol Mol, E-28006 Madrid, Spain
关键词
primary biliary cirrhosis; lymphocyte activation; adhesion molecules; angiogenesis; vascular endothelial growth factor; angiopoietins;
D O I
10.1016/j.jhep.2004.09.024
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: 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; beta(2)-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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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页码:124 / 131
页数:8
相关论文
共 61 条
[1]  
Battista S, 2001, AM J GASTROENTEROL, V96, P869
[2]   ICAM-3 INTERACTS WITH LFA-1 AND REGULATES THE LFA-1/ICAM-1 CELL-ADHESION PATHWAY [J].
CAMPANERO, MR ;
DELPOZO, MA ;
ARROYO, AG ;
SANCHEZMATEOS, P ;
HERNANDEZCASELLES, T ;
CRAIG, A ;
PULIDO, R ;
SANCHEZMADRID, F .
JOURNAL OF CELL BIOLOGY, 1993, 123 (04) :1007-1016
[3]   Direct cell adhesion to the angiopoietins mediated by integrins [J].
Carlson, TR ;
Feng, YZ ;
Maisonpierre, PC ;
Mrksich, M ;
Morla, AO .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (28) :26516-26525
[4]   INVOLVEMENT OF THE CD4 MOLECULE IN A POST-ACTIVATION EVENT ON T-CELL PROLIFERATION [J].
CARRERA, AC ;
SANCHEZMADRID, F ;
LOPEZBOTET, M ;
BERNABEU, C ;
DELANDAZURI, MO .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1987, 17 (02) :179-186
[5]   TRIGGERING OF T-CELL PROLIFERATION THROUGH AIM, AN ACTIVATION INDUCER MOLECULE EXPRESSED ON ACTIVATED HUMAN-LYMPHOCYTES [J].
CEBRIAN, M ;
YAGUE, E ;
RINCON, M ;
LOPEZBOTET, M ;
DELANDAZURI, MO ;
SANCHEZMADRID, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 168 (05) :1621-1637
[6]  
DEEG HJ, 1984, ANNU REV MED, V35, P11, DOI 10.1146/annurev.med.35.1.11
[7]   CD105 is important for angiogenesis: evidence and potential applications [J].
Duff, SE ;
Li, CG ;
Garland, JM ;
Kumar, S .
FASEB JOURNAL, 2003, 17 (09) :984-992
[8]  
EGGINK HF, 1982, CLIN EXP IMMUNOL, V50, P17
[9]   The biology of VEGF and its receptors [J].
Ferrara, N ;
Gerber, HP ;
LeCouter, J .
NATURE MEDICINE, 2003, 9 (06) :669-676
[10]   Intrahepatic enhanced expression of β2-microglobulin conformational epitope in acute liver allograft rejection evidence of modulation by glucocorticoids [J].
García-Monzón, C ;
Majano, PL ;
Solís, JA ;
Rodríguez, S ;
Colina, F ;
López-Botet, M ;
Moreno-González, E ;
Moreno-Otero, R .
DIGESTIVE DISEASES AND SCIENCES, 1998, 43 (08) :1755-1762