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Immune electron microscopic study of hepatitis B virus associated antigens in hepatocytes

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Summary

In order to elucidate the localization of HBV-associated antigens including nonstructural forms, immune electron microscopic study was carried out in liver tissues obtained from 96 cases of chronic liver diseases with persistent HBs antigenemia and asymptomatic HBsAg carriers.

The results obtained were as follows.

  1. 1)

    HBsAg was localized in the cytoplasm with two different patterns: an intracytoplasmic localization and a diffuse membranous localization.

  2. 2)

    Most cases showing membranous localization of HBsAg were associated with HBeAg in serum and the existence of core and Dane particles in the hepatocytes.

  3. 3)

    Antigenicity of HBsAg was found on the outer coat of Dane particles and cisternal membrane of dilated endoplasmic reticulum (ER) in addition to the plasma membrane. Some of the antigen positive ER were detected close to the plasma membrane, suggesting that the membranous localization of HBsAg was presumably resulted from the exocytosis of the antigen positive ER. These findings suggest that HBsAg expressed on the plasma membrane is a very likely target antigen in the course of cytolysis mediated by immunological mechanism.

  4. 4)

    HBcAg and HBeAg were localized in the cytosol of the hepatocyte in addition to the nucleus, but never found on the plasma membrane.

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References

  1. Barry RB, et al: Viral Immunology and Immunopathology. ed by Notkins AL, Academic Press, p 113, 1975

  2. William HB, Anthony CA: Surface antigens of viral-infected cells. In “Virus Infection and the Cell Surface”, ed by G. Poste, GL Nicolson. Amsterdam, North-Holland, 1977

    Google Scholar 

  3. Dane DS, et al: Virus-like particles in serum of patients with Australia-antigen associated hepatitis. Lancet I: 695, 1970

    Article  Google Scholar 

  4. Yoshizawa H, et al: Demonstration of hepatitis B e antigen in hepatitis B core particles obtained from the nucleus of hepatocytes infected with hepatitis B virus. J Gen Virol 42: 513, 1979

    Article  PubMed  CAS  Google Scholar 

  5. Takahashi K, et al: Demonstration of hepatitis B e antigen in the core of Dane particles. J Immunol 122: 275, 1979

    PubMed  CAS  Google Scholar 

  6. Kamimura T, et al: Electron microscopic studies of hepatitis B antigen in liver tissue. J Clin Electron Microscopy 11: 29, 1978

    Google Scholar 

  7. Kamimura T, et al: Electron microscopic studies of Dane particles in hepatocytes with specific reference to intracellular development of Dane particles and their relation with HBe antigen in serum. Hepatology 1: 392, 1981

    Article  PubMed  CAS  Google Scholar 

  8. Sasaki H, et al: Ultrastructural study of interaction of lymphocytes and hepatocytes bearing hepatitis B antigen. In “Frontiers in Liver Disease”, ed by Berk PD, Chalmers TC, Georg Thieme Verlag Stuttgart, New York, 1981, pp 171–176

    Google Scholar 

  9. Takahashi K, et al: Demonstration of c antigen and antibody to e by means of passive hemagglutination method. J Immunol 119: 1556, 1977

    PubMed  CAS  Google Scholar 

  10. Nakane PK, Pierce GB: Enzyme-labeled antibodies for the light and electron microscopic localization of tissue antigens. J Cell Biol 33: 307, 1967

    Article  PubMed  CAS  Google Scholar 

  11. Nakane PK, Kawaoi A: Peroxidase-labeled antibody. A new method of conjugation. J Histchem Cytochem 22: 1084, 1974

    CAS  Google Scholar 

  12. Mclean IW, Nakane PK: Periodate-lysine-paraformaldehyde fixative: A new fixative for immunoelectron microscopy. J Histchem Cytochem 22: 1077, 1974

    CAS  Google Scholar 

  13. Shikata T, et al: Staining methods of Australia antigen in paraffin section. Jpn J Exp Med 44: 25, 1974

    PubMed  CAS  Google Scholar 

  14. Gerber MA, et al: Electron microscopy and immunoelectron microscopy of cytoplasmic hepatitis B antigen in hepatocytes. Am J Path 75: 489, 1974

    PubMed  CAS  Google Scholar 

  15. Yamada G, et al: Hepatitis B core and surface antigens in liver tissue. Light and electron microscopic localization by the peroxidase-labeled antibody method. Lab Invest 36: 649, 1977

    PubMed  CAS  Google Scholar 

  16. Huang SN, et al: Immunohistologic demonstration of hepatitis B viral antigens in liver with reference to its significance in liver injury. Lab Invest 40: 1, 1979

    PubMed  CAS  Google Scholar 

  17. Nielsen JO, et al: Incidence and meaning of the “e” determinant among hepatitis B antigen positive patients with acute and chronic liver diseases. Lancet II: 913, 1974

    Article  Google Scholar 

  18. Trepo C, et al: Detection of e antigen by immunofluorescence in cytoplasm of hepatocytes of HBsAg carriers. Lancet I: 486, 1976

    Article  Google Scholar 

  19. Arnold W, et al: Localization of e antigen in nuclei of hepatocytes in HBsAg positive liver disease. Gut 19: 994, 1977

    Article  Google Scholar 

  20. Ray MB, et al: Distribution patterns of hepatitis B surface antigen (HBsAg) in the liver of hepatitis patients. J CIin Path 29: 94, 1976

    Article  CAS  Google Scholar 

  21. Gudat F, Bianchi L: HBsAg: A target antigen on the liver cell? In “Membrane Alterations as Bases of Liver Injury”, ed by Popper H, et al. MTP press-London, p 171, 1977

    Google Scholar 

  22. Gudat F, Bianchi L: Evidence for phasic sequences in nuclear HBcAg formation and cell membrane directed flow of core particles in chronic hepatitis B. Gastroenterology 73: 1194, 1977

    PubMed  CAS  Google Scholar 

  23. Trevisan A, et al: Relationship between membrane bound immunoglobulin and viral antigens in liver cells from patients with hepatitis B virus infection. Gastroenterology 77: 209, 1979

    PubMed  CAS  Google Scholar 

  24. Trevisan A, et al: Core antigen-specific immunoglobulin G bound to the liver cell membrane in chronic hepatitis B. Gastroenterology 82: 218, 1982

    PubMed  CAS  Google Scholar 

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This work was partly supported by a Scientific Research Grant to H. Sasaki (Project No. 56480161) from the Ministry of Education, Science and Culture of Japan.

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Kojima, T. Immune electron microscopic study of hepatitis B virus associated antigens in hepatocytes. Gastroenterol Jpn 17, 558–575 (1982). https://doi.org/10.1007/BF02779134

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  • DOI: https://doi.org/10.1007/BF02779134

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