Costimulatory Signaling Sulfamethoxazole Stimulate Dendritic Cell Sulfamethoxazole and Its Metabolite Nitroso
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منابع مشابه
Drug antigenicity, immunogenicity, and costimulatory signaling: evidence for formation of a functional antigen through immune cell metabolism.
Recognition of drugs by immune cells is usually explained by the hapten model, which states that endogenous metabolites bind irreversibly to protein to stimulate immune cells. Synthetic metabolites interact directly with protein-generating antigenic determinants for T cells; however, experimental evidence relating intracellular metabolism in immune cells and the generation of physiologically re...
متن کاملHLA-DQ restricted activation of nitroso-sulfamethoxazole-specific CD4+ T-lymphocytes
Background Sulfamethoxazole hypersensitivity has been used as a paradigm to study the role of drug metabolism in the activation of T-cells. CD4+ T-cells isolated from blood/ skin of 100% of hypersensitive patients are activated with the protein-reactive metabolite nitroso sulfamethoxazole (SMX.NO). Since SMX.NO binds to multiple cellular proteins it is assumed that peptides derived from the mod...
متن کاملRecognition of sulfamethoxazole and its reactive metabolites by drug-specific CD4+ T cells from allergic individuals.
The recognition of the antibiotic sulfamethoxazole (SMX) by T cells is usually explained with the hapten-carrier model. However, recent investigations have revealed a MHC-restricted but processing- and metabolism-independent pathway of drug presentation. This suggested a labile, low-affinity binding of SMX to MHC-peptide complexes on APC. To study the role of covalent vs noncovalent drug presen...
متن کاملEffect of arylhydroxylamine metabolites of sulfamethoxazole and dapsone on stress signal expression in human keratinocytes.
The initiation of an immune response to small molecules is believed to require the release of stress/danger signals that activate resident dendritic cells, presumably secondary to the formation of reactive metabolites. We hypothesized that exposure to arylhydroxylamine metabolites of dapsone and sulfamethoxazole lead to the expression/release of numerous stress signals in the skin. To test this...
متن کاملThe relationship between the disposition and immunogenicity of sulfamethoxazole in the rat.
Idiosyncratic toxicity associated with sulfamethoxazole (SMX) is thought to be a consequence of bioactivation to the hydroxylamine metabolite (SMX-NOH) and further oxidation to the ultimate reactive metabolite, nitroso-sulfamethoxazole (SMX-NO). To establish the link between the formation of the ultimate reactive metabolite and SMX hypersensitivity, we have undertaken metabolism and immunogenic...
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