The effect of pertussis toxin on mediator release from human basophils

We have found that basophils (n = 9) treated with pertussis toxin (1.0 μg/ml) fail to respond to a subsequent challenge with either 1.0 μM f-Met peptide (p < 0.0005) or 0.24 μg/ml of C5a (p < 0.0005) although their responses to anti-IgE (0.1 μg/ml) and A23187 (1.0 μg/ml) were unaltered. These results were confirmed in purified (average purity = 89 ± 3%) basophils (n = 4). Leukotriene C₄ release was also reduced to 15 ± 5% of control (p < 0.005) when pertussis toxin-treated basophils were exposed to 1.0 μM f-Met peptide, although no inhibition was noted when anti-IgE or A23187 were used as the stimuli. The effect of pertussis toxin on basophils appears to be independent of the presence of contaminating mononuclear cells. We found that pertussis toxin inhibited f-Met peptide-induced histamine release regardless of the magnitude of the stimulus (0.01 μM to 1.0 μM f-Met peptide), although anti-IgE-induced release was unaffected over a dose-response curve. The effect of pertussis toxin was found to both time- and concentration-dependent. The maximum effects were obtained after a 3-hr incubation with 1 μg/ml of toxin. Lower (0.01 to 0.05 μg/ml) concentrations of toxin or shorter (30 to 60 min) incubation periods did not significantly (p > 0.05) inhibit mediator release.