Influence of Glutathione Conjugation on the Immunogenicity of Dinitrophenyl Derivatives in the Rat
Malcolm Drummond Tingle, Janet B. Clarke, N.R. Kitteringham, B.K. Park
Abstract
Malcolm Drummond Tingle, Janet B. Clarke, N.R. Kitteringham, B.K. Park
Abstract
The role of metabolic detoxication (glutathione conjugation) in the humoral response to three model haptens, dinitrofluorobenzene (DNFB), dinitrochlorobenzene (DNCB) and dinitrobenzenesulphonate (DNBS), was investigated in male Wistar rats. All three haptens produced a measurable anti-dinitrophenyl IgG antibody response over a wide dose range (2.7 nmol/kg to 0.27 mmol/kg) given for 4 days. A significant difference in antibody titre was only observed at the highest dose (DNFB greater than DNCB = DNBS), despite a marked difference in reactivity towards a protein carrier (albumin) and N-acetyl-lysine in vitro. These observations can be partly explained by the fact that the most reactive hapten (DNFB) conjugates most rapidly with glutathione in vitro and in vivo.
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The role of metabolic detoxication (glutathione conjugation) in the humoral response to three model haptens, dinitrofluorobenzene (DNFB), dinitrochlorobenzene (DNCB) and dinitrobenzenesulphonate (DNBS), was investigated in male Wistar rats. All three haptens produced a measurable anti-dinitrophenyl IgG antibody response over a wide dose range (2.7 nmol/kg to 0.27 mmol/kg) given for 4 days. A significant difference in antibody titre was only observed at the highest dose (DNFB greater than DNCB = DNBS), despite a marked difference in reactivity towards a protein carrier (albumin) and N-acetyl-lysine in vitro. These observations can be partly explained by the fact that the most reactive hapten (DNFB) conjugates most rapidly with glutathione in vitro and in vivo.
Key concepts: Dinitrophenyl, Immunogenicity, Glutathione, Immunology, Chemistry, Xenobiotic, Biology, Medicine