OBJECTIVES: In this study we examined the effects of the inflammatory agent hydrogen peroxide (H2O2) on IgE-mediated mast cell responses. MATERIALS AND METHODS: Release of preformed granular mediators and newly synthesised TNF-alpha were measured in the RBL-2H3 mast cell line stimulated through IgE receptors (FcepsilonRI) in the presence of varying concentrations of H2O2. The sensitivity of the intracellular calcium response to H2O2 exposure was investigated. RESULTS: We found that H2O2 treatment impaired the release of preformed and newly synthesised mediators. H2O2 treatment simultaneously led to a profound inhibition of the calcium response. Calcium fluxes from both intra- and extracellular sources were impaired. H2O2 action was dependent on the intracellular redox state. Receptor activation directly stimulated intracellular H2O2 production. CONCLUSION: While in many cells H2O2 induces potent inflammatory responses we show that it can be an anti-inflammatory agent by not only inhibiting the release of preformed mediators but also by affecting the secretion of newly synthesized TNF-alpha. Inhibition is a consequence of the profound effect on intracellular calcium levels. The activation of an intracellular oxidative burst by FcepsilonRI aggregation and the sensitivity of intracellular responses to redox-altering agents point to an important regulatory mechanism of mast cell responses in inflammatory tissues.
OBJECTIVES: In this study we examined the effects of the inflammatory agent hydrogen peroxide (H2O2) on IgE-mediated mast cell responses. MATERIALS AND METHODS: Release of preformed granular mediators and newly synthesised TNF-alpha were measured in the RBL-2H3 mast cell line stimulated through IgE receptors (FcepsilonRI) in the presence of varying concentrations of H2O2. The sensitivity of the intracellular calcium response to H2O2 exposure was investigated. RESULTS: We found that H2O2 treatment impaired the release of preformed and newly synthesised mediators. H2O2 treatment simultaneously led to a profound inhibition of the calcium response. Calcium fluxes from both intra- and extracellular sources were impaired. H2O2 action was dependent on the intracellular redox state. Receptor activation directly stimulated intracellular H2O2 production. CONCLUSION: While in many cells H2O2 induces potent inflammatory responses we show that it can be an anti-inflammatory agent by not only inhibiting the release of preformed mediators but also by affecting the secretion of newly synthesized TNF-alpha. Inhibition is a consequence of the profound effect on intracellular calcium levels. The activation of an intracellular oxidative burst by FcepsilonRI aggregation and the sensitivity of intracellular responses to redox-altering agents point to an important regulatory mechanism of mast cell responses in inflammatory tissues.