[Proposed mechanism of action of metalloendopeptidase-F in the treatment of patients with chronic hepatitis B or C infection].

Abstract

Chronic hepatitis B and C virus infections have been characterized by the pathophysiological features with a high incidence of progression to cirrhosis and development of hepatocellular carcinoma. The viral persistence produced by escape mutations from virus-specific cytotoxic T lymphocytes (CTL) response may lead to upregulation of delayed-type hypersensitivity immune response, which causes hepatic tissue damage through non specific macrophage activation and CTL response and promotes pathogenesis of hepatic fibrosis. In a preliminary clinical study, a novel metalloendopeptidase-F (MEP-F) has been shown to be effective in the treatment of patients with either chronic hepatitis B or C infection. Oral administration of MEP-F resulted in a significant reduction of the serum levels of HBs antigen and HCV RNA and improvement in the liver function abnormalities. However, the mechanism of action of MEP-F is not yet well understood. There are accumulating evidences showing an important role of alpha 2-macroglobulin-proteinase complexes in regulatory mechanisms of immune response and repairing within impaired and inflammatory tissues. In this article, reviewing the pharmacological and biological properties of alpha 2-macroglobulin-proteinase complexes, the mechanism of anti-viral effect of MEP-F is examined based on the clinical findings. It is indicated that alpha 2-macroglobulin-MEP-F complexes may induce macrophage/Kuppfer cell activation and proliferation through binding their receptors on the cells and activating signaling cascades, which enhance both anti-viral specific and nonspecific immune responses. alpha 2-Macroglobulin-MEP-F complexes may also augment cellular immunity and hepatic regeneration by neutralizing the immunosuppressive and fibrogenic activities of transforming growth factor-beta.

• Authors: S Fujisaki, T Fujisaki, J Yoshida, Y Fujisaki, M Mitani, M Nakamura, N Otake
• Journal: The Japanese journal of antibiotics (Jpn J Antibiot) Vol. 53 Issue 3 Pg. 135-56 (Mar 2000) ISSN: 0368-2781 [Print] Japan
• PMID: 10834146 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Cytokines
• Low Density Lipoprotein Receptor-Related Protein-1
• Receptors, Immunologic
• Transforming Growth Factor beta
• alpha-Macroglobulins
• Metalloendopeptidases
• metalloendopeptidase F

Topics

• Animals
• Cytokines (metabolism, physiology)
• Hepatitis B, Chronic (immunology, therapy)
• Hepatitis C, Chronic (immunology, therapy)
• Humans
• Liver (metabolism, physiology)
• Liver Regeneration
• Low Density Lipoprotein Receptor-Related Protein-1
• Macrophages (immunology)
• Metalloendopeptidases (metabolism, pharmacology, therapeutic use)
• Receptors, Immunologic (metabolism, physiology)
• T-Lymphocytes, Cytotoxic (immunology)
• Transforming Growth Factor beta (antagonists & inhibitors)
• alpha-Macroglobulins (metabolism, physiology)