1993 Fiscal Year Final Research Report Summary
Significance of adhesion molecules in hepatic fibrosis.
| Project/Area Number |
03670381
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
YAMAUCHI Masayoshi The Jikei University School of Medicine, 1st Dept of Med.Assistant Professor, 医学部, 講師 (20138811)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUHARA Yuji The Jikei University School of Medicine, 1st Dept of Med., Assistant
OHATA Mituru The Jikei University School of Medicine, 1st Dept of Med., Assistant (50231204)
HIRAKAWA Junnichi The Jikei University School of Medicine, 1st Dept of Med., Assistant (00231548)
NAKAJIMA Hisato The Jikei University School of Medicine, 1st Dept of Med., Assistant (90207788)
TODA Gotaro The Jikei University School of Medicine, Ist Dept of Med.Professor, 医学部, 教授 (40090500)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Hepatic fibrosis / Integrin / Adhesion molecule / ICAM-1 / VCAM-1 / Fibronectin receptor / Vitronectin receptor / VNR |
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| Research Abstract |
The Adhesion molecules such as integrin subfamilies are engaged in interactions with various extracellular matrix components such as collagen, laminin, fibronectin and vitronectin. In this study, we clarified the significance of adhesion molecules in patients with hepatic fibrosis.
1. Pooles sera collected from cirrhotic patients was fractionated by affinity chromatography with monoclonal antibodies against integrin beta 1 and beta 3. Western immunoblotting of eluates showed that integrin beta 1 and beta 3 were present in human serum.
2. We developed sandwich enzyme-linked immunosorbent assay (ELISA) for integrin beta 1 or beta 3. The serum level of integrin was significantly higher in patients with chronic active hepatitis, liver cirrhosis when compared with healthy subjects. The increase in the serum level of integrin beta 1 was associated with the severity of liver diseases, especially with the hepatic fibrosis. The serum level of integrin beta 3 also increased in patients with chroni
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c liver diseases. However, no correlation was observed between serum levels of integrin beta 3 and the degree of fibrosis, necrosis or degeneration. Immunohistochemicalstudies showed that a strong staining for integrin beta 1 was evident on fibrotic areas, and on the plasma membranes of hepatocytes and sinusoidal lining cells. Integrin beta 3 was expressed in sinusoidal lining cells, platelets, vascular endothelial cells and arterial walls and on the plasma membranes of hepatocytes. However, no anti- beta 3 staining was present in fibrotic area. In conclusion, the serum level of integrin beta 1 in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.
3. Human platelets also contain a vitronectin receptor ( alpha v beta 3). We revealed that integrin beta 3 of platelet was significantly higher in chronic hepatitis and liver cirrhosis than in the healthy subjects.
4. Serum levels of intercellular adhesion molecule-1 (ICAN-1), a ligand for alpha L beta 2(LFA-1) and vascular adhesion molecule-1 (VCAM-1), a ligand for alpha 4 beta 1 (VLA-4), were significantly higher in the patients with alcoholic hepatitis and cirrhosis than in the non-ciirhotic alcoholic liver disease and the healthy subjects. Furthermore, only the serum level of ICAM-1 was significantly higher in the patients with alcoholic hepatitis than in those with alcoholic cirrhosis. These data showed that ICAM-1/LFA-1 interaction may be more important in the development of alcoholic hepatitis. Less
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