NDLI: The Antirheumatic Drug Gold, a Coin With Two Faces: AU(I) and AU(III).Desired and Undesired Effects on the Immune System

Content Provider	PubMed Central
Author	Takahashi, Kazuo Griem, Peter Goebel, Carsten Gonzalez, Jose Gleichmann, Ernst
Copyright Year	1994
Abstract	Three new findings are reviewed that help to understand the mechanisms ofaction of antirheumatic Au(I) drugs, such as disodium aurothiomalate (Na2Au(I)TM):(i) We found that Na2Au(I)TM selectively inhibits T cell receptor (TCR)-mediatedantigen recognition by murine CD4+ T cell hybridomas specific for antigenic peptidescontaining at least two cysteine residues. Presumably, Au(I) acts as a chelatingagent forming linear complexes (Cys-Au(I)-Cys) which prevent correct antigen-processingand/or peptide recognition by the TCR. (ii) We were able to show thatAu(I) is oxidized to Au(III) in phagocytic cells, such as macrophages. Because Au(III)is re-reduced to Au(I) this may introduce an Au(I)/Au(III) redox system into phagocyteswhich scavenges reactive oxygen species, such as OCl- and inactivateslysosomal enzymes. (iii) Pretreatment with Au(III) of a model protein antigen, bovineribonuclease A (RNase A), induced novel antigenic determinants recognized byCD4+ T lymphocytes. Analysis of the fine specificity of these ‘Au(III)-specific’ T cellsrevealed that they react to RNase peptides that are not presented to T cells when thenative protein, i.e., not treated with Au(III), is used as antigen. The T cell recognitionof these cryptic peptides did not require the presence of gold. This finding hasimportant implications for understanding the pathogenesis of allergic and autoimmuneresponses induced by Au(I) drugs. Taken together, our findings indicate thatAu(I) and Au(III) each exert specific effects on several distinct components ofmacrophages and the subsequent activation of T cells; these effects may explainboth the desired anti-inflammatory and the adverse effects of antirheumatic golddrugs.
Related Links	http://dx.doi.org/10.1155/mbd.1994.483
Ending Page	496
Page Count	14
Starting Page	483
File Format	PDF
ISSN	07930291
Journal	Metal-Based Drugs
Issue Number	5-6
Volume Number	1
Language	English
Publisher	Hindawi Publishing Corporation
Publisher Date	1994-01-01
Access Restriction	Open
Rights Holder	Hindawi Publishing Corporation
Subject Keyword	Toxicology Inorganic Chemistry Pharmacology Drug Discovery Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Toxicology Pharmacology Inorganic Chemistry

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