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Canadian Journal of Gastroenterology
Volume 13, Issue 9, Pages 721-727
Original Article

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

Ikuko Haruta,1 Katsutoshi Tokushige,1 Tatsuji Komatsu,2 Ikuo Ikeda,3 Katsumi Yamauchi,1 and Naoaki Hayashi1

1Division of Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
2Yokohama National Hospital, Yokohama-shi, Kanagawa-ken, Japan
3Second Department of Pathology, Tokyo Women’s Medical University, Tokyo, Japan

Received 3 July 1998; Accepted 1 December 1998

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


OBJECTIVES: To clarify the role of adhesion molecule in liver cell injury.

PATIENTS AND 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 immunohistological 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.