Advertisement

Inflammation Research

, Volume 44, Issue 11, pp 482–485 | Cite as

Auranofin inhibits calcium uptake into opsonized-zymosan-stimulated neutrophils obtained from rats

  • K. Ishitani
  • A. Matsuura
  • H. Honda
Article

Abstract

In order to study the pharmacological action site of auranofin during the functional suppression of leukocytes, especially neutrophils, we investigated the influence of auranofin on the calcium-45 (45Ca2+) uptake into peripheral blood neutrophils and peritoneal resident macrophages isolated from normal and adjuvant-induced arthritis (AA) rats. Calcium-45 uptake into neutrophils and macrophages obtained from normal and AA rats was increased by stimulation with opsonized-zymosan, while auranofin inhibited the increase in the45Ca2+ uptake into neutrophils, but not into macrophages. There was a tendency that auranofin more strongly inhibited the increase in the45Ca2+ uptake into neutrophils obtained from AA rats than normal rats, but no statistically significant difference between them was observed in the inhibitory potency of auranofin. From these results, it is suggested that auranofin would show anti-rheumatic and anti-inflammatory effects by the inhibition of Ca2+ uptake into neutrophils which infiltrate into local lesions during the early and active phases of rheumatoid arthritis.

Key words

Auranofin Calcium uptake Neutrophils Macrophages 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Fujitsu T, Sakuma S, Seki N, Senoh H, Mori J, Kikuchi H. Effect of auranofin on autoimmune disease in a mouse model. Int J Immunopharmacol 1986;8:897–910.PubMedGoogle Scholar
  2. [2]
    Griswold DE, Lee JC, Poste G, Hanna N. Modulation of macrophage-lymphocyte interaction by the antiarthritic gold compound, auranofin. J Rheumatol 1985;12:490–7.PubMedGoogle Scholar
  3. [3]
    Dimartino MJ, Walz DT. Interaction of lysosomal enzyme release from rat leukocytes by auranofin. A new chrysotherapeutic agent. Inflamm 1977;2:131–42.Google Scholar
  4. [4]
    Davis P, Miller CL, Russell AS. Effects of gold compounds on the function of phagocytic cells. I. Suppression of phagocytosis and generation of chemiluminescence by polymorphonuclear leukocytes. J Rheumatol Suppl 1982;8:18–24.PubMedGoogle Scholar
  5. [5]
    Ikeda K, Ishigaki M, Wu D, Sunose H, Suzuki M, Ishitani K, et al. Intracellular Ca2+ responses induced by acetylcholine in the submucosal nasal acinar gland cells in guinea pig. J Physiol 1995;268:L361–7.Google Scholar
  6. [6]
    Alonso-Torre SR, Trautmann A. Calcium responses elicited by nucleotides in macrophages. J Biol Chem 1993;268:18640–7.PubMedGoogle Scholar
  7. [7]
    Cattaneo MG, Gullo M, Vicentini LM. Ca2+ and Ca2+ channel antagonists in the control of human small cell lung carcinoma cell proliferation. Eur J Pharmacol 1993;247:325–31.PubMedGoogle Scholar
  8. [8]
    White JP, Naccache PH, Molski TFP, Borgeat P, Sha'afi RI. Direct demonstration of increased intracellular concentration of free calcium in rabbit and human neutrophils following stimulation by chemotactic factor. Biochem Biophys Res Commun 1983;113:44–50.PubMedGoogle Scholar
  9. [9]
    Korchak HM, Vienne K, Rutherford LE, Weissman G. Neutrophil stimulation receptor, membrane and metabolic events. Fed Proc 1984;43:2749–54.PubMedGoogle Scholar
  10. [10]
    West BC, Rosental AS, Gelb NS, Kimball HR. Separation and characterization of human neutrophil granules. Am J Pathol 1974;77:41–66.PubMedGoogle Scholar
  11. [11]
    Drysdale BE, Yapundich RA, Shin ML, Shin HS. Lipopolysaccharide-mediated macrophage activation: The role of calcium in the generation of tumoricidal activity. J Immunol 1987;138:951–6.PubMedGoogle Scholar
  12. [12]
    Ishitani K, Ogawa S, Suzuki M. Influence of arachidonate metabolism on enhancement of intracellular transglutaminase activity in mouse peritoneal macrophages. J Biochem 1988;104:397–402.PubMedGoogle Scholar
  13. [13]
    Ishitani K, Suzuki M. Influence of transglutaminase on the functions of mouse peritoneal macrophages. Microbiol Immunol 1989;33:59–68.PubMedGoogle Scholar
  14. [14]
    Toskos GC. Immunomodulatory treatment in patients with rheumatoid disease: Mechanisms of action. Semin Arthritis Rheum 1987;17:24–38.PubMedGoogle Scholar
  15. [15]
    Veys EM, Hermans P, Goldstain G, King P, Schindler J, Van Wauve J. Determination of T lymphocyte subpopulations by monoclonal antibodies in rheumatoid arthritis; Influence of immunomodulation agents. Int J Immunopharmacol 1981;3:313–9.PubMedGoogle Scholar
  16. [16]
    Venables P. Epstein-Barr virus infection and autoimmunity in rheumatoid arthritis. Ann Rheum Dis 1988;47:265–9.PubMedGoogle Scholar
  17. [17]
    Naides SJ, Field HE. Transient rheumatoid factor positivity in acute human parvovirus B-19 infection. Arch Intern Med 1988;148:2587–9.PubMedGoogle Scholar
  18. [18]
    Hafstrom I, Uden AM, Palmblad J. Modulation of neutrophil functions by auranofin. Studies on effects in vitro and in rheumatoid arthritis patients. Scand J Rheumatol 1983;12:97–105.PubMedGoogle Scholar
  19. [19]
    Hafstrom I. The effect of auranofin on polymorphonuclear granulocytes. Scand J Rheumatol Suppl 1983;51:36–41.PubMedGoogle Scholar
  20. [20]
    DiMartino MJ, Walz DT. Effect of auranofin on antibody-dependent cellular cytotoxicity (ADCC) mediated by rat peripheral blood polymorphonuclear leukocytes and mononuclear cells. Inflamm 1980;4:279–88.Google Scholar
  21. [21]
    Wong K, Parente J, Prasad LVS, Ng D. Auranofin modulated cytoplasmic free calcium in neutrophils by mobilizing intracellular calcium and inhibiting protein kinase C. J Biol Chem 1990;265:21454–61.PubMedGoogle Scholar
  22. [22]
    Minty CA, Hall ND, Bacon PA. Depressed exocytosis by rheumatoid neutrophils in vitro. Rheumatol Int 1983;3:139–42.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel 1995

Authors and Affiliations

  • K. Ishitani
    • 1
  • A. Matsuura
    • 2
  • H. Honda
    • 1
  1. 1.Research Laboratories IIGrelan Pharmaceutical Co. Ltd.Hamura-cityJapan
  2. 2.Collaboration Group, Research CenterGrelan Pharmaceutical Co. Ltd.Hamura-cityJapan

Personalised recommendations