Clinical implication of vascular cell adhesion molecule-1 and very late activation antigen-4 interaction, and matrix metalloproteinase-2 production in patients with liver disease.
OBJECTIVE
To clarify the role of adhesion molecule in liver cell injury.


METHODS
The serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), and the expression of VCAM-1 and its ligand, very late activation antigen-4 (VLA-4), were examined in patients with various liver diseases. In addition, the presence of matrix metalloproteinase-2 (MMP-2) was investigated because the release of MMP-2 is thought to be mediated by VLA-4-positive cells. sVCAM-1 and MMP-2 were measured by ELISA assay, and VCAM-1 and VLA-4 were studied by immuno-histological methods.


RESULTS
In acute hepatitis (AH) patients, the serum level of sVCAM-1 was significantly elevated compared with that in other cohorts. VCAM-1 was expressed on sinusoidal lining cells but not on hepatocytes. In patients with chronic liver disease, sVCAM-1 levels rose in concert with the progression of chronic hepatitis (CH), and VCAM-1 was also expressed. VLA-4 was detected in both mononuclear cells and Kupffer cells in AH livers, but mainly in Kupffer cells in patients with CH. In AH patients, MMP-2 levels were similar to those in control subjects, but in CH and liver cirrhosis patients, MMP-2 level was elevated in association with CH progression.


CONCLUSIONS
The immune response through the VCAM-1 and VLA-4 pathways is important in hepatocyte injury, especially in AH patients, to attach VLA-4-positive mononuclear cells to VCAM-1-positive sinusoidal lining cells. The distribution of VLA-4-positive cells differs between AH and CH patients. VLA-4-positive Kupffer cells in chronic liver diseases might be involved in the progression of CH, perhaps through the mechanism of upregulation of MMP-2 production.
Haruta
I
I
Division of Medicine, Tokyo Women's Medical University, Japan. ikuko@kt.rim.or.jp
Tokushige
K
K
Komatsu
T
T
Ikeda
I
I
Yamauchi
K
K
Hayashi
N
N
D000208:Acute Disease; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000097:blood / Q000502:physiology*; D008107:Liver Diseases / Q000097:blood / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D016201:Receptors, Lymphocyte Homing / Q000097:blood / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000502:physiology*
D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D020778:Matrix Metalloproteinase 2