Mechanism of Protective Effect of Prostaglandin E in Murine Hepatitis Virus Strain 3 Infection: Effects on Macrophage Production of Tumour Necrosis Factor, Procoagulant Activity and Leukotriene B4

  • S. Sinclair
  • M. Abecassis
  • P. Y. Wong
  • A. Romaschin
  • L. S. Fung
  • G. Levy
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 276)


Murine hepatitis virus strain 3 (MHV-3) produces a strain dependent spectrum of liver disease. Mice of the A strain are fully resistant whereas Balb/cJ mice die of fulminant hepatic failure (1) . The susceptibility of inbred mice to MHV-3, is dependent on host factors which are under strict genetic control. Differences in viral replication both invivo and in-vitro do not appear to account for strain-dependent differences in resistance to MHV-3 and it has been suggested that variation in susceptibility/resistance of inbred mice reflects defects in the host–s immune response (2). Experimental ablation of the immune cell populations by X irradiation (3) , antilymphocyte serum (4) , or infection with frog virus-3 (5) renders resistant A/J mice susceptible. Furthermore, reconstitution of susceptible neonatal A/J mice with adult immune cells requires both T lymphocytes and an adherent cell population (6) . More recently, it has been demonstrated that clearance of virus from the central nervous system is dependent upon the presence of both CD4+ and CD8+ cells that recognize viral antigens in the context of H-2D gene products (7).


Peritoneal Macrophage Procoagulant Activity Mouse Hepatitis Virus 17CL1 Cell Murine Hepatitis Virus 
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  1. 1.
    Levy, G.A., Leibowitz, J.L., Edgington, T.S. 1982. Lymphocyte-instructed monocyte induction of the coagulation pathways parallels the induction of hepatitis by the murine hepatitis virus. Prog. Liver Dis. 7:393–409.PubMedGoogle Scholar
  2. 2.
    MacNaughton, M.R. and S. Patterson. 1980. Mouse hepatitis virus strain 3 infection of C57, A/Sn and A/J strain mice and their macrophages. Arch. Virol. 66:71.PubMedCrossRefGoogle Scholar
  3. 3.
    Dindzans, V.J., MacPhee, P., Fung, L.S., Leibowitz, J.L. and Levy, G.A. 1985. The immune response to mouse hepatitis virus: Expression of monocyte procoagulant activity and plasminogen activator during infection in vivo. J. Immunol. 135:4189.PubMedGoogle Scholar
  4. 4.
    Dupuy, J.M., Levy-Leblond, E., Le Provest, C. 1975. Immunopathology of mouse hepatitis virus type 3 infection. II. Effect of immunosuppression in resistant mice. J. Immunol. 114: 226.PubMedGoogle Scholar
  5. 5.
    Pereira, C.A, Steffan, A.M. and Kirn, A. 1984. Kupffer and endothelial liver cell damage renders A/J mice susceptible to mouse hepatitis virus type 3. Virus Res. 1:557.PubMedCrossRefGoogle Scholar
  6. 6.
    Levy-Leblond, E. and Dupuy, J.M. 1977. Neonatal susceptibility to MHV-3 infection in mice. I. Transfer of resistance. J. Immunol. 118:1219.PubMedGoogle Scholar
  7. 7.
    Sussman, M.A., Shubin, R.A., Kyuwa, S. and Stohlman, S.A. 1989. T-cell mediated clearance of mouse hepatitis virus strain JHM from the central nervous system. J. Virol. 63:3051–3056.PubMedGoogle Scholar
  8. 8.
    Dindzans, V.J., Zimmerman, B., Sherker, A. and Levy, G.A. 1987. Susceptibility to mouse hepatitis virus strain 3 in Balb/cJ mice: Failure of immune cell proliferation and interleukin 2 production, in: Coronaviruses, Michael M.C. Lai and Stephen A. Stohlman, ed., Plenum Publishing Corp, New York.Google Scholar
  9. 9.
    Levy, G.A. and Abecassis, M. 1989. Activation of the immune coagulation system by murine hepatitis virus strain 3. The Reviews of Infectious Diseases. 11:S712-S721.CrossRefGoogle Scholar
  10. 10.
    Dindzans, V.J., Skamene, E. and Levy, G.A. 1986. Susceptibility/resistance to mouse hepatitis virus strain 3 and macrophage procoagulant activity are genetically linked and controlled by two non-H-2-linked genes. J. Immunol. 137: 2355–60.PubMedGoogle Scholar
  11. 11.
    Abecassis, M., Falk, J.A., Makowka, L., Dindzans, V.J., Falk, R.E. and Levy, G.A. 1987. 16, 16 dimethyl prostaglandin E2 prevents the development of fulminant hepatitis and blocks the induction of monocyte/macrophage procoagulant activity after murine hepatitis virus strain 3 infection. J. Clin. Invest. 80:881–889.PubMedCrossRefGoogle Scholar
  12. 12.
    Stern, D.M. and Nawroth, P.P. 1986. Modulation of endothelial hemostatic properties by tumor necrosis factor. J. Exp. Med. 163:740–45.PubMedCrossRefGoogle Scholar
  13. 13.
    Kunkel, S.L., Wiggins, R.C., Chensue, S.W. and Larrick, J. 1986. Regulation of macrophage tumor necrosis factor production by prostaglandin E2. Biochem. and Biophys. Res. Comm. 137:404–410.Google Scholar
  14. 14.
    Hagmann, W., Steffan, A., Kirn and Keppler, D. 1987. Leukotrienes as mediators in frog virus 3-induced hepatitis in rats. Hepatology. 7:732–736.PubMedCrossRefGoogle Scholar
  15. 15.
    MacPhee, P.J., Dindzans, V.J., Fung, L.S. and Levy, G.A. 1985. Acute and chronic changes in the microcirculation of the liver in inbred strains of mice following infection with mouse hepatitis virus type 3. Hepatology. 5:649–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Levy, G.A., Leibowitz, J.L., Edgington, T.S. 1981. Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice. J. Exp. Med. 154:1150–63.PubMedCrossRefGoogle Scholar
  17. 17.
    Beutler, B. and Cerami, A. 1989. The biology of cachectin/TNF-A primary mediator of the host response. Ann. Rev. Immunol. 7:625–55.CrossRefGoogle Scholar
  18. 18.
    Bachwich, P.R., Chensue, S.W., Larrick, J.W., Kunkel, S.L. 1986. Tumor necrosis factor stimulates interleukin-1 and prostaglandin E2 production in resting macrophages. Biochem. Biophys. Res. Commun. 136:94–101.PubMedCrossRefGoogle Scholar
  19. 19.
    Keppler, D., Huber, M. and Baumert T. 1988. Leukotrienes as mediators in diseases of the liver. Seminars in Liver Disease. 8:357–366.PubMedCrossRefGoogle Scholar
  20. 20.
    Ham, E.A., Soderman, D.D., Zanetti, M.E., Dougherty, H.W., McCauley E, Kuehl Jr., F.A. 1983. Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc. Natl. Acad. Sci. USA. 80:4349–4353.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • S. Sinclair
    • 1
  • M. Abecassis
    • 1
  • P. Y. Wong
    • 2
  • A. Romaschin
    • 2
  • L. S. Fung
    • 1
  • G. Levy
    • 1
  1. 1.Department of MedicineUniversity of TorontoTorontoCanada
  2. 2.Department of BiochemistryUniversity of TorontoTorontoCanada

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