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Treatment of Resistant A/J Mice with Methylprednisolone (MP) Results in Loss of Resistance to Murine Hepatitis Strain 3 (MHV-3) and Induction of Macrophage Procoagulant Activity (PCA)

  • R. J. Fingerote
  • J. L. Leibowitz
  • Y. S. Rao
  • G. A. Levy
Chapter
  • 179 Downloads
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 380)

Abstract

BALB/cJ mice die of fulminant hepatitis within 7 days of exposure to murine hepatitis virus strain 3 (MHV-3) whereas A/J mice are fully resistant to the lethal effects of MHV-3 infection. Previous studies have implicated macrophage activation with production of a unique macrophage prothrombinase (PCA) and lymphocyte cytokine secretion in the pathogenesis of MHV-3 susceptibility and have demonstrated that immunosuppression induces susceptibility in resistant mice. This study was undertaken to determine whether macrophages, derived from resistant A/J mice and treated in vitro with methylprednisolone sodium succinate (MP), elaborated PCA following MHV-3 exposure and whether therapy with MP altered resistance of A/J mice to MHV-3 infection in vivo.

Macrophages, incubated with MP in vitro, expressed dose dependent increases in PCA following infection with MHV-3. No induction of PCA occurred in macrophages treated with MHV-3 or MP alone. Analysis of mRNA transcripts for mouse fibrinogen like protein (musfiblp), the MHV-3 specific prothrombinase, in macrophages which were incubated with MP prior to exposure to MHV-3 demonstrated significantly increased mRNA levels as compared to macrophages not incubated with MP prior to MHV-3 exposure. In vivo, A/J mice treated for 3 days with 500 mg/kg/day of MP prior to infection with MHV-3 demonstrated extensive hepatocyte necrosis and fibrin deposition in hepatic sinusoids on histological examination of liver tissue, elevated serum transaminases and 100% mortality within 10 days of infection. These results therefore provide further support for the role of increased PCA in the pathogenesis of MHV-3 related liver necrosis.

Keywords

Fulminant Hepatitis Fibrin Deposition Plaque Form Unit Hepatic Sinusoid Susceptible Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • R. J. Fingerote
    • 1
  • J. L. Leibowitz
    • 2
  • Y. S. Rao
    • 1
  • G. A. Levy
    • 1
  1. 1.Department of MedicineThe Toronto Hospital, University of TorontoTorontoCanada
  2. 2.Department of PathologyUniversity of Texas Health Sciences CenterHoustonUSA

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