BIOMAT Database Logo BIOMAT Database Logo

Effect of auranofin, a new antiarthritic agent, on immune complex-induced release of lysosomal enzymes from human leukocytes. 1977

A E Finkelstein, and F R Roisman, and D T Walz

Auranofin, an oral chrysotherapeutic agent effective in the treatment of rheumatoid arthritis (RA), was found to be a potent, noncytotoxic inhibitor of IgG-RF immune complex-induced lysosomal enzyme release (LER) from human leukocytes. At a concentration of 1 microg Au/ml (5 microM), auranofin produced a marked reduction in beta-glucuronidase (100%), acid phosphatase (88%), and lysozyme (72%) release. In contrast, gold sodium thiosulfate (GST, an injectable gold compound) had no inhibitory activity on LER at equivalent gold concentrations (i.e., 1 microg Au/ml) and only modest activity (less than 36% inhibition) at concentrations as high as 40 microg Au/ml. The 50% inhibitory dose (LD50) of auranofin on LER was calculated to be 3-4 microM (0.6-0.8 microg Au/ml). Blood gold levels in auranofin-treated RA patients were found to be within the range required for in vitro inhibition of LER, and correlated with decreases in IgG, RF titers, and IgG-RF immune-complex formation in vitro. These results suggest that the therapeutic action of auranofin may be caused, at least in part, by inhibition of LER and/or decreases in immune-complex formation.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D009942 Organometallic Compounds A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed) Metallo-Organic Compound,Metallo-Organic Compounds,Metalloorganic Compound,Organometallic Compound,Metalloorganic Compounds,Compound, Metallo-Organic,Compound, Metalloorganic,Compound, Organometallic,Compounds, Metallo-Organic,Compounds, Metalloorganic,Compounds, Organometallic,Metallo Organic Compound,Metallo Organic Compounds
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D006046 Gold A yellow metallic element with the atomic symbol Au, atomic number 79, and atomic weight 197. It is used in jewelry, goldplating of other metals, as currency, and in dental restoration. Many of its clinical applications, such as ANTIRHEUMATIC AGENTS, are in the form of its salts.
D006052 Gold Sodium Thiomalate A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis. Aurothiomalate,Gold Thiomalate,Sodium Gold Thiomalate,Aurolate,Gold Disodium Thiomalate, Monohydrate,Gold Thiomalic Acid,Mercaptobutanedioic Acid Monogold(1+) Sodium Salt,Miocrin,Miocrisin,Monogold (1+) Disodium Thiomalate,Myochrysine,Myocrisin,Myocrysine,Sodium Aurothiomalate,Sodium Thiomalatoaurate,Tauredon,Aurothiomalate, Sodium,Gold Thiomalate, Sodium,Sodium Thiomalate, Gold,Thiomalate, Gold,Thiomalatoaurate, Sodium
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000936 Antigen-Antibody Complex The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES. Immune Complex,Antigen-Antibody Complexes,Immune Complexes,Antigen Antibody Complex,Antigen Antibody Complexes,Complex, Antigen-Antibody,Complex, Immune,Complexes, Antigen-Antibody,Complexes, Immune
D012217 Rheumatoid Factor Autoantibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS. Factor, Rheumatoid

Related Publications

A E Finkelstein, and F R Roisman, and D T Walz
Inhibition of lysosomal enzyme release from rat leukocytes by auranofin. A new chrysotherapeutic agent.
June 1977, Inflammation,
A E Finkelstein, and F R Roisman, and D T Walz
Effect of sodium thiomalate on immune complex-induced release of lysosomal enzymes from human polymorphonuclear leucocytes.
February 1986, Immunopharmacology,
A E Finkelstein, and F R Roisman, and D T Walz
Studies of the effect of auranofin, a new antiarthritic agent, on platelet aggregation.
March 1982, Inflammation,
A E Finkelstein, and F R Roisman, and D T Walz
Release of lysosomal enzymes from human polymorphonuclear leukocytes by soluble intermediate immune complexes.
January 1978, Scandinavian journal of rheumatology,
A E Finkelstein, and F R Roisman, and D T Walz
Effect of anti-rheumatic drugs on the release of lysosomal enzymes from human leukocytes.
January 1984, Zeitschrift fur Rheumatologie,
A E Finkelstein, and F R Roisman, and D T Walz
The release of lysosomal enzymes from human polymorphonuclear leukocytes by human C3e.
February 1984, Clinical immunology and immunopathology,
A E Finkelstein, and F R Roisman, and D T Walz
Cytochalasin B: effect on lysosomal enzyme release from human leukocytes.
March 1973, Proceedings of the National Academy of Sciences of the United States of America,
A E Finkelstein, and F R Roisman, and D T Walz
Trypanosoma cruzi: parasite-induced release of lysosomal enzymes by human polymorphonuclear leukocytes.
October 1983, Experimental parasitology,
A E Finkelstein, and F R Roisman, and D T Walz
Modification of zymosan-induced release of lysosomal enzymes from human polymorphonuclear leukocytes by cytochalasin B.
September 1974, The Journal of cell biology,
A E Finkelstein, and F R Roisman, and D T Walz
[Release of lysosomal enzymes from rabbit polymorphonuclear leukocytes (author's transl)].
January 1979, Bratislavske lekarske listy,
Copied contents to your clipboard!