Integrin up-regulation in chronic liver disease: relationship with inflammation and fibrosis in chronic hepatitis C.
In 94 patients with chronic hepatitis C, the pattern of integrin expression was correlated with firstly, the histological activity index, necro-inflammatory grade, and stage of fibrosis; secondly, the expression of inflammatory markers including ICAM-1; and thirdly, the extent and intensity of laminin deposition in the perisinusoidal matrix. Immunohistochemical results were evaluated according to a semi-quantitative scoring system or by image analysis. Increased beta1 expression was observed in 88.2% of cases. The expression of alpha1 and alpha5 was increased in 55% and 58.5% of cases, respectively. alpha6 chain was detected in 78.7% of cases. There were no statistically significant differences in integrin expression level according to Knodell's score, inflammatory grade, or stage of fibrosis. ICAM-1 expression was higher in patients with high scores for beta1 expression, but the differences were not statistically significant. There were significantly more patients with high scores for beta1 expression among those with continuous perisinusoidal deposition of laminin. Moreover, a close statistical correlation was observed between alpha6 induction and perisinusoidal laminin deposition (p<0.001). The results suggest that integrin up-regulation in chronic hepatitis C is more closely related to the fibrotic process than to the inflammatory lesions. This reinforces the idea that integrin induction in chronic liver disease is part of a coordinated process involved in the progression of liver fibrosis.
Nejjari
M
M
Laboratoire de Biologie Cellulaire, Unité INSERM U327, Faculté de Médecine Xavier Bichat, Paris, France.
Couvelard
A
A
Mosnier
J F
JF
Moreau
A
A
Feldmann
G
G
Degott
C
C
Marcellin
P
P
Scoazec
J Y
JY
D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D006684:HLA-DR Antigens; D016023:Integrins; D007797:Laminin; D018799:Intercellular Adhesion Molecule-1