The role of hydrogen peroxide in basophil histamine release and the effect of selected flavonoids

Abstract

Studies on hydrogen peroxide (H2O2)-induced histamine release from human basophils indicate that H2O2 is a weak stimulus of histamine release, that the release process is Ca2+ and energy-dependent, and that histamine release is not influenced by theophylline (in keeping with previous observations with rat mast cells). Low concentrations of H2O2 appeared to augment and high concentrations to inhibit histamine release induced by anti-IgE. However, the inhibitory effect of high concentrations of H2O2 were completely abrogated by catalase, which destroys H2O2, and thus indicates that basophils retain immunologic responsivity and are not irreversibly effected by high concentrations of H2O2. Leukocyte suspensions relatively enriched in monocytes, lymphocytes, basophils, neutrophils, and neutrophils plus eosinophils were prepared by Percoll-gradient centrifugation. Anti-IgE stimulated H2O2 formation only in the fraction richest in basophils. Opsonized zymosan, on the other hand, stimulated H2O2 generation in both the basophil and monocyte fractions, indicating activation of both monocytes and basophils by this stimulus. Mixtures of basophil-containing leukocyte suspensions plus purified neutrophils and opsonized zymosan stimulated histamine release in proportion to concomitant generation of H2O2. Addition of catalase reduced histamine release under these conditions, whereas scavengers of other toxic oxygen derivatives (superoxide dismutase, alpha-tocopherol, D-mannitol) had little or no effect on histamine release. These findings suggest that neutrophil-derived H2O2 can cause basophil histamine release in mixed populations of activated leukocytes. Three naturally occurring flavonoids, quercetin, apigenin, and taxifolin (dihydroquercetin) were examined for their effect on anti-IgE-induced histamine release and H2O2 generation in basophil-containing leukocyte suspensions.(ABSTRACT TRUNCATED AT 250 WORDS)