Abstract
The effect of sodium aurothiomalate and auranofin on the generation of superoxide anions (O −2 ) by polymorphonuclear leukocytes (PMNLs) and adherent mononuclear phagocytic cells (AMNCs) has been investigated. Sodium aurothiomalate at final concentrations of 1, 10, and 100 μg Au/ml and auranofin ranging from 0.1 to 2.0 μg Au/ml were used in the reactions involving all celt types. Results have been compared between cells drawn from normal controls and patients with active rheumatoid disease. The effect of gold compounds on both cell types was assessed following activation by phorbyl myristate acetate (1×10−8 M) and N-formyl-methionylleucyl-phenylalanine (1×10−4 M) using a cytochromec reduction method. Sodium aurothiomalate at the maximum concentration modestly inhibited O −2 generation by PMNLs but not AMNCs. Auranofin inhibits O −2 generation by both cell types. Inhibition of cells from patients with rheumatoid arthritis was greater than that seen with cells from normal controls.
Similar content being viewed by others
References
Davis, P., C. L. Miller, andA. S. Russell. 1982. Effects of gold compounds on the function of phagocytic cells. I. Suppression of phagocytosis and the generation of chemiluminescence by polymorphonuclear leukocytes.J. Rheumatol. 9(Snppl. 8): 18–24.
Ho, P. P., A. L. Young, andG. L. Southard. 1978. Methyl ester of N-formyl-methionylleucyl-phenylalanine. Chemotactic responses of human blood monocytes and inhibition of gold compounds.Arthritis Rheum. 21:133–136.
Wolach, B., J. E. DoBoard, R. L. Baehner, andL. A. Boxer. 1981. Modulation of leucocyte aggregation and degranulation by gold compounds.Fed. Proc. 40:753.
Davis, P., C. Johnston, C. L. Miller, et al. 1983. Effects of gold compounds on the function of phagocytic cells. II. Inhibition of Superoxide radical generation of tripeptide activated polymorphonuclear leukocytes.Arthritis Rheum. 26:82–86.
Greenwald, R. A. 1981. Oxy radicals and connective tissue.J. Rheumalol. 8:185–187 (editorial).
Harth, M., P. A. Keown, andJ. F. Orange. 1983. Monocyte-dependent excited oxygen radical generation in rheumatoid arthritis: Inhibition by gold sodium thiomalate.J. Rheumatol. 10:701–707.
Boyum, A. 1968. Isolation of mononuclear cells and granulocytes from human blood.Scand. J. Clin. Lab. Invest. 21(Suppl. 97):77–89.
Kumagai, K., K. Itoh, S. Hinuma, andM. Tada. 1979. Pretreatment of plastic petri dishes with fetal calf serum. A simple method for macrophage isolation.J. Immunol. Methods 29:17–25.
Kronenberg, L. H., H. M. Rosenblatt, Y. Bryson, andL. H. Merigan. 1982. Interferon: Immunobiology and clinical significance.Ann. Intern. Med. 96:80–93.
Rabinovitch, M., S. I. Hamburg, andH. B. Fleit. 1980. Interferon-induced enhancement of Fc receptor-medicated macrophage phagocytosis.J. Reticuloendothelial Soc. 28(Suppl.):27s-28s.
Cohen, H. J., andM. E. Chovaniec. 1978. Superoxide production by digitonin stimulated guinea pig granulocytes. The effects ofN-ethyl maleimide, divalent cations, and glycolytic and mitochondrial inhibitors on the activation of the Superoxide generating system.J. Clin. Invest. 401:1088–1096.
McCord, J. M., I. Fridovich. 1969. Superoxide dismutase. An enzyme function for erythrocuprein (hemocuprein).J. Biol. Chem. 244:6049–6055.
Williams, L. T., R. Snyderman, M. C. Pike, andR. J. Lefkowitz. 1977. Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes.Proc. Natl. Acad. Sci. U.S.A. 74:1204–1208.
Feinberg, H., H. Michel, G. V. R. Born. 1974. Determination of the fluid volume of platelets by their separation, through silicone oil.J. Lab. Clin. Med. 84:926–934.
Wacker, W. E. C., D. D. Ulmer, andB. L. Vallee. 1956. Metalloenzymes and myocardial infarction. II. Malic and lactic dehydrogenase activites and zinc concentrations in serum.N. Engl. J. Med. 255:449–456.
Petrone, W. F., D. K. English, K. Wong, andJ. M. McCord. 1980. Free radicals and inflammation: Superoxide-dependent activation of a neutrophil chemotactic factor in plasma.Proc. Natl. Acad. Sci. U.S.A. 77:1159–1163.
Johnston, R. B., J. E. Lehmeyer. 1976. Elaboration of toxic oxygen by products by neutrophils in a model of immune complex disease.J. Clin. Invest. 57:836–841.
Simchowitz, L., J. Mehta, andI. Spilberg. 1979. Chemotactic factor induced generation of Superoxide radicals by human neutrophils: Effect of metabolic inhibitors and antiinflammatory drugs.Arthritis Rheum. 271:755–763.
Hafström, I., A. Uden, andJ. Palmblad. 1983. Modulation of neutrophil functions by auranofin.Scand. J. Rheumatol. 12:97–105.
Coates, T. D., B. Wolach, D. Y. Tzeng, C. Higgins, R. L. Baehner, andL. A. Boxer. 1983. The mechanism of action of the antiinflammatory agents dexamethasone and auranofin in human polymorphonuclear leukocytes.Blood 62:1070–1077.
Hafström, I., B. E. Seligmann, M. M. Friedman, andJ. I. Gallin. 1984. Auranofin affects early events in human polymorphonuclear neutrophil activation by receptor-medicated stimuli.J. Immunol 132:2007–2014.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Davis, P., Johnston, C. Effects of gold compounds on function of phagocytic cells. Inflammation 10, 311–320 (1986). https://doi.org/10.1007/BF00916126
Issue Date:
DOI: https://doi.org/10.1007/BF00916126