Advertisement

Inhibition of in Vitro Lymphocyte Proliferation and B Cell Differentiation by Deoxyguanosine: Evidence for Separate Mechanisms

  • L. J. M. Spaapen
  • M. E. Dane
  • E. Toebes
  • B. Tepas
  • G. E. J. Staal
  • M. Duran
  • W. Kuis
  • G. T. Rijkers
  • B. J. M. Zegers
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

A number of patients with a selective cellular immunodeficiency associated with a deficiency of purine nucleoside Phosphorylase (PNP) have been described (1,2). In PNP deficiency, one of the accumulated substrates of the enzyme i.e. deoxyguanosine (dGuo) appears to be extremely toxic to lymphoid cells in particular to thymocytes (3). The proposed pathophysiologic mechanism in PNP deficiency implies lymphocyte “specific” phosphorylation of dGuo into dGTP which inhibits the reduction of CDP by ribonucleotide reductase; as a result intracellular dCTP is depleted leading to a disturbance of lymphocytic DNA synthesis (4). In vitro studies e.g. on lymphoblastoid cell lines have shown that dGuo inhibits the in vitro growth of T cell lines whereas B cell lines are relatively unaffected(5,6). Most studies have not been performed under PNP-deficient conditions.

Keywords

Peripheral Blood Lymphocyte Lymphocyte Proliferation Lymphoblastoid Cell Line Ribonucleotide Reductase Normal Lymphocyte 
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.

References

  1. 1.
    J.W. Stoop, B.J.M. Zegers, G.F.M. Hendrickx, L.H. Siegenbeek van Heukelom, C.E.J. Staal, P.K. de Bree, S.K. Wadman and R.E. Ballieux. N.Engl.J.Med.296: 651 (1977).PubMedCrossRefGoogle Scholar
  2. 2.
    A.J. Ammann. In: Enzyme Defects and Immune Dysfunction, Ciba Found. Symp. 68: 55, Excerpta Medica, Amsterdam (1979).Google Scholar
  3. 3.
    D.A Carson, J. Kaye and J.E. Seegmiller. Proc.Natl.Acad.Sci.USA 74: 5677 (1977).PubMedCrossRefGoogle Scholar
  4. 4.
    D.W. Martin Jr. and E.W. Gelfand.Ann.Rev.Biochem.50: 845 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    B.S Mitchell, E. Mejias, P.E. Daddona and W.N. Kelley. Proc.Natl. Acad.Sci.USA 75: 5011 (1978).PubMedCrossRefGoogle Scholar
  6. 6.
    T.-S Chan. Cell. 14: 523 (1978).PubMedCrossRefGoogle Scholar
  7. 7.
    C.J Heijnen, F. UytdeHaag, F.H.J. Gmelig-Meyling and R.E. Ballieux. Cell.Immunol. 43: 282 (1979).PubMedCrossRefGoogle Scholar
  8. 8.
    R.H Stevens, C.J. Thiele and A. Saxon. Immunology 36: 407 (1979).PubMedGoogle Scholar
  9. 9.
    R.A. De Abreu, J.M. van Baal, J.A.J.M. Bakkeren, C.H.M.M. de Bruyn and E.D.A.M. Schretlen. J.Chromatogr. 227: 45 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    A.R. Hayward. Clin.Exp. Immunol. 41: 141 (1980).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • L. J. M. Spaapen
    • 1
  • M. E. Dane
    • 1
  • E. Toebes
    • 1
  • B. Tepas
    • 2
  • G. E. J. Staal
    • 3
  • M. Duran
    • 2
  • W. Kuis
    • 1
  • G. T. Rijkers
    • 1
  • B. J. M. Zegers
    • 1
  1. 1.Department of ImmunologyUniversity Children’s Hospital, “Het Wilhelmina KinderziekenhuisUtrechtThe Netherlands
  2. 2.Department of Metabolic DiseasesUniversity Children’s Hospital, “Het Wilhelmina KinderziekenhuisUtrechtThe Netherlands
  3. 3.Department of Medical EnzymologyState University HospitalUtrechtThe Netherlands

Personalised recommendations