Advertisement

Selective Inhibition of Cytotoxic T Lymphocyte Proliferation by Mizoribine (Bredinin), an Adenosine Analog

  • Tomoko Hasunuma
  • Hisashi Yamanaka
  • Chihiro Terai
  • Nobuyuki Miyasaka
  • Naoyuki Kamatani
  • Kusuki Nishioka
  • Kiyonobu Mikanagi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 253A)

Abstract

Since a number of patients with severe combined immunodeficiency syndrome have been found to be deficient in adenosine deaminase (ADA) or purine nucleotide phosphorylase (PNP)(1, 2), purine metabolism has been postulated to be deeply involved in human immune system. A series of evidences has shown that abnormally accumulated purine deoxynucleosides in these patients have selective toxicity on T or B lymphocytes. Another experiments demonstrated critical roles of purine enzymes on lymphocyte maturation or differentiation. (3, 4, 5).

Keywords

Peripheral Blood Lymphocyte Lymphocyte Subpopulation Mycophenolic Acid Purine Metabolism Purine Analog 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. 1.
    E.R. Giblett, J.E. Anderson, F. Cohen, et al. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet ii: 1067–1069 (1972)CrossRefGoogle Scholar
  2. 2.
    E.R. Giblett, A.J. Ammann, D.W. Wara, et al. Nucleoside phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet i: 1010–1013 (1975)CrossRefGoogle Scholar
  3. 3.
    M. Massaia, D.D.F. Ma, T.A. Sylwestrowicz, et al. Enzymes of purine metabolism in human peripheral lymphocyte subpopulations. Clin. Exp. Immunol. 50: 148–154 (1982)PubMedGoogle Scholar
  4. 4.
    D.D.F. Ma, T.A. Sylwestrowicz, S. Granger, et al. Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes. J. Immunol. 129: 1430–1435 (1982)PubMedGoogle Scholar
  5. 5.
    A.V. Hoffbrand, D.D.F. Ma and A.D.B. Webster. Enzyme patterns in normal lymphocyte subpopulations, lymphoid leukemias and immunodeficiency syndromes. Clin. Heamatol. 11: 719–741 (1982)Google Scholar
  6. 6.
    J.A. van Boxel and S.A. Paget. Predominantly T-cell infiltrate in rheumatoid synovial membranes. N. Engl. J. Med. 293: 517–520 (1975)PubMedCrossRefGoogle Scholar
  7. 7.
    M. Goto, T. Miyamoto, K. Nishioka, et al. Selective loss of suppressor T cells in rheumatoid arthritis patients: Analysis of peripheral blood lymphocytes by 2-demensional flow cytometry. J. Rheumatol. 13: 853–857 (1986)PubMedGoogle Scholar
  8. 8.
    O. Duke, G.S. Panayi, G. Janossy, et al. Analysis of T cell subsets in the peripheral blood and synovial fluid of patients with rheumatoid arthritis by means of monoclonal antibodies. Ann. Rheum. Dis. 42: 357–361 (1983)PubMedCrossRefGoogle Scholar
  9. 9.
    T. Inou. Immunosuppressive effects of bredinin on renal transplantation-summarized by bredinin research committee-. Ishoku 17: 547–561 (1982)Google Scholar
  10. 10.
    H. Koyama and M. Tsuji. Genetic and biochemical studies on the activation and cytotoxic mechanism of bredinin, a potent inhibitor of purine biosynthesis in mammalian cells. Biochem. Pharmac. 32: 3547–3553 (1983)CrossRefGoogle Scholar
  11. 11.
    K. Sakaguchi, M. Tsujino, M. Yoshizawa, et al. Action of bredinin on mammalian cells. Cancer Res. 35: 1643–1648 (1975)PubMedGoogle Scholar
  12. 12.
    T.J. Franklin and J.M. Cook. The inhibition of nucleic acid synthesis by mycophenolic acid. Biochem. J. 113: 515–524 (1969)PubMedGoogle Scholar
  13. 13.
    D.G. Streeter, J.T. Witkowski, G.P. Khare, et al. Mechanism of action of 1-b-D-ribofuranosyl-1, 2-4-triazole-3-carboxamide (virazole), a new broad-spectrum antiviral agent. Proc. Natl. Acad. Sci. U.S.A. 70: 1174–1178 (1973)PubMedCrossRefGoogle Scholar
  14. 14.
    P.A. Furman, J.A. Fyfe, M.H. St. Clair, et al. Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proc. Natl. Acad. Sci.USA 83: 8333–8337 (1986)PubMedCrossRefGoogle Scholar
  15. 15.
    D.A. Carson, E. Lakow, D.B. Wasson, et al. Lymphocyte dysfunction caused by deficiencies in purine metabolism. Immunol. Today 234-238 (1981)Google Scholar
  16. 16.
    G. Weber. Medical progress; Enzymology of cancer cells. N. Engl. J. Med. 296: 486–493, 541-551 (1977)PubMedCrossRefGoogle Scholar
  17. 17.
    C.M. Smith, L.J. Fontenelle, H. Muzik, et al. Inhibitors of inosinate dehydrogenase activity in Enrich ascites tumor cells in vitro. Biochem. Pharmacol. 23: 2727–2735 (1974)PubMedCrossRefGoogle Scholar
  18. 18.
    H.J. Lee, K. Pawlak, B.T. Nguyen, et al. Biochemical differences among four inosinate dehtdrogenase inhibitors, mycophenolic acid, ribavirin, tiazofurin and selenazofurin, studied in mouse lymphoma cell culture. Cancer Res. 45: 5512–5520 (1985)PubMedGoogle Scholar
  19. 19.
    R.K. Robino, G.R. Revankar, P.A. McKerman, et al. The importance of IMP dehydrogenase inhibition in the broad spectrum antiviral activity of ribavirin and selenazofurin. Adv. in Enzyme Regulation. 24: 29–43 (1986)CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Tomoko Hasunuma
    • 1
  • Hisashi Yamanaka
    • 1
  • Chihiro Terai
    • 1
  • Nobuyuki Miyasaka
    • 1
  • Naoyuki Kamatani
    • 1
  • Kusuki Nishioka
    • 1
  • Kiyonobu Mikanagi
    • 1
  1. 1.Institute of RheumatologyTokyo Women’s Medical CollegeTokyoJapan

Personalised recommendations