Inhibitory Mechanism of Mizoribine on the Antibody Production of Mouse B Cells Stimulated with Lipopolysaccharide

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Author(s)

Abstract

It has been reported that the immunosuppressant mizoribine (MZR)inhibits T cell proliferation by depleting intracellular guanine nucleotides via competitive inhibition of inosine 5''-monophosphate (IMP)dehydrogenase in the purine metabolism pathway. This study was performed to determine if the mechanism by which MZR suppresses the proliferation of mouse B cells and antibody production by these cells is dependent on the depletion of intracellular guanine nucleotides. Stimulation of purified splenic B cells of mice with lipopolysaccharide (LPS), a mitogen to B cells, increased both proliferation and antibody production. MZR suppressed both of these functions in a dose-dependent fashion. MZR also caused a decrease in the amount of intracellular guanosine 5''-triphosphate (GTP). When the cultures were grown on plates containing guanosine plus 8-aminoguanosine, the amount of intracellular GTP, which had been reduced by MZR, was restored. Furthermore, the repletion of GTP pools restored both proliferation and antibody production almost to their previous levels. These results suggest that MZR suppresses antibody production and proliferation of B cells by acting directly on B cells. Furthermore, it is suggested that the inhibitory effect of MZR on antibody production, as well as on T cell proliferation, is dependent on the decrease in intracellular guanine nucleotide pools of mouse B cells.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 74(4), 323-330, 1997-08-01

    The Japanese Pharmacological Society

References:  23

Cited by:  3

Codes

  • NII Article ID (NAID)
    10008679518
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4287828
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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