Skip to main content
SpringerLink
Log in

Effect of auranofin on antibody-dependent cellular cytotoxicity (ADCC) mediated by rat peripheral blood polymorphonuclear leukocytes and mononuclear cells

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Auranofin and other clinically used gold compounds were evaluated in vitro for effects on antibody-dependent cellular cytotoxicity (ADCC)of L929 fibroblast target cells mediated by adjuvant rat peripheral blood PMNs or mononuclear cells. Auranofin (10ΜM) was found to be a potent inhibitor of PMNADCC. In contrast, gold sodium thiomalate (10–100ΜM), gold thioglucose (10–1000ΜM, and nongold substructures of auranofin (10ΜM) were not inhibitory. In continuous culture, gold sodium thiomalate and relatively low concentrations of auranofin (≤1 ΜM) significantly enhanced PMNADCC. Results of pretreatment studies indicate that auranofin's inhibitory activity of PMNADCC is caused by a noncytotoxic effect on PMN function which is not associated with alteration of PMN-target cell contact. In contrast to its inhibitory activity on PMNADCC, auranofin pretreatment of mononuclear cells resulted in enhanced target cell destruction which appeared to correlate with increased mononuclear cell-target cell contact.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Walz, D. T., M. J. Dimartino, L. W. Chakrin, B. M. Sutton, andA. Misher. 1976. Antiarthritic properties and unique pharmacological profile of a potential chrysotherapeutic agent: SK&F D-39162.J. Pharmacol. Exp. Ther. 197:142.

    Google Scholar 

  2. Finkelstein, A. E., D. T. Walz, V. Batista, M. Misraji, F. Roisman, andA. Misher. 1976. Auranofin. New oral gold compound for treatment of rheumatoid arthritis.Ann. Rheum. Dis. 35:251.

    Google Scholar 

  3. Berglöf, F.-E., K. Berglöf, andD. T. Walz. 1978. Auranofin: An oral chrysotherapeutic agent for the treatment of rheumatoid arthritis.J. Rheum. 5:68.

    Google Scholar 

  4. Weisman, M. H., andD. M. Hannifin. 1979. Management of rheumatoid arthritis with oral gold.Arthritis Rheum. 22:922.

    Google Scholar 

  5. Walz, D. T., M. J. Dimartino, andD. E. Griswold. 1979. Immunopharmacology of auranofin and gold sodium thiomalate: Effects on humoral immunity.J. Rheum. 6 (Suppl. 5):74.

    Google Scholar 

  6. DiMartino, M. J., andD. T. Walz. 1977. Inhibition of lysosomal enzyme release from rat leukocytes by auranofin. A new chrysotherapeutic agent.Inflammation 2:131.

    Google Scholar 

  7. Finkelstein, A. E., F. R. Roisman, andD. T. Walz. 1977. The effect of auranofin, a new antiarthritic agent, on immune complex-induced release of lysosomal enzymes from human leukocytes.Inflammation 2:143.

    Google Scholar 

  8. Walz, D. T., andD. E. Griswold. 1978. Immunopharmacology of gold sodium thiomalate and auranofin (SK&F D-39162): Effects on cell-mediated immunity.Inflammation 3:117.

    Google Scholar 

  9. Lorber, A., T. M. Simon, J. Leeb, A. Peter, andS. A. Wilcox. 1979. Effect of chrysotherapy on parameters of immune response.J. Rheum. 6(Suppl. 5):82.

    Google Scholar 

  10. Finkelstein, A. E., O. R. Burrone, D. T. Walz, andA. Misher, 1977. Effect of auranofin on DNA and protein synthesis in human lymphocytes.J. Rheum. 4:245.

    Google Scholar 

  11. Simon, T. M., D. H. Kunishima, G. J. Vibert, andA. Lorber. 1979. Cellular antiproliferative action exerted by auranofin.J. Rheum. 6(Suppl. 5):91.

    Google Scholar 

  12. Lorber, A., S. A. Wilcox, G. J. Vibert, andT. M. Simon. 1979. Carbon rod atomization analysis: Application to in vivo lymphocyte gold quantitation.J. Rheum. 6(Suppl. 5):31.

    Google Scholar 

  13. Walz, D. T., D. E. Griswold, M. J. DiMartino, andE. E. Bumbier. 1979. Distribution of gold in blood following administration of auranofin (SK&F D-39162).J. Rheum. 6 (Suppl. 5):56.

    Google Scholar 

  14. Winchurch, R. A., G. V. Foschi, andD. T. Walz. 1974. Inhibition of the lymphocytemediated cytotoxic reaction by anti-inflammatory drugs.J. Reticuloendothel. Soc. 15:112.

    Google Scholar 

  15. Boyum, A. 1968. Isolation of mononuclear cells and granulocytes from human blood.Scand. J. Clin. Lab. Invest. 21(suppl. 97):77.

    Google Scholar 

  16. Walz, D. T., M. J. DiMartino, J. H. Kuch, andW. Zuccarello. 1971. Adjuvant-induced arthritis in rats. I. Temporal relationship of physiological, biochemical and hematological parameters.Proc. Soc. Exp. Biol. Med. 136:907.

    Google Scholar 

  17. Lovchik, J. C., andR. Hong. 1977. Antibody-dependent cell-mediated cytolysis (ADCC): Analyses and projections.Prog. Allergy 22:1.

    Google Scholar 

  18. Clark, R. A., andS. J. Klebanoff. 1975. Neutrophil-mediated tumor cell cytotoxicity: Role of the peroxidase system.J. Exp. Med. 141:1442.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Smith Kline & French Laboratories, 1500 Spring Garden Street, 19101, Philadelphia, Pennsylvania

    M. J. DiMartino & D. T. Walz

Authors
  1. M. J. DiMartino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. T. Walz
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

SK&F D-39162 (2,3,4,6-tetra-O-acetyl-l-thio-Β-d-glucopyranosato-S)triethylphosphine gold.

Rights and permissions

Reprints and permissions

About this article

Cite this article

DiMartino, M.J., Walz, D.T. Effect of auranofin on antibody-dependent cellular cytotoxicity (ADCC) mediated by rat peripheral blood polymorphonuclear leukocytes and mononuclear cells. Inflammation 4, 279–288 (1980). https://doi.org/10.1007/BF00915029

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00915029

Keywords

Search

Navigation