Maitotoxin, a novel activator of mediator release from human basophils, induces large increases in cytosolic calcium resulting in histamine, but not leukotriene C4, release

Maitotoxin (MTX) is a potent marine toxin which stimulates several Ca⁺⁺- dependent processes presumably through an increase in Ca⁺⁺ permeability. We have examined the effect of MTX on the release of chemical mediators from human basophils and its mechanism of action. MTX (1-20 ng/ml) induced histamine release (37-100%) from both mixed leukocyte preparations and purified basophils. Histamine release activated by MTX was slow (t( 1/2 ) ≃ 15 min), temperature and Ca⁺⁺ dependent (optimal at 37°C and 1-2.5 mM Ca⁺⁺). Sr⁺⁺ ion could substitute for Ca⁺⁺ in the secretory process. Digital video microscopy analysis of purified (>70%) basophils revealed that MTX (1-20 ng/ml) induced a slow and marked increase of cytosolic Ca⁺⁺ levels that was temporally coincident with histamine release. MTX (1-20 ng/ml) stimulated the release of sulfidopeptide leukotriene C₄ from mixed leukocyte preparations (≃0.5% basophils). However, purified basophils (77 ± 7%) showed no sulfidopeptide leukotriene C₄ release even in the presence of large histamine secretion (84 ± 14%). Two organic Ca⁺⁺-channel entry blockers, verapamil and diltiazem (1-30 μM) inhibited the release of histamine induced by MTX, whereas the dihydropyridine nifedipine (0.1-10 μM) caused only minimal inhibition. These results suggest that MTX represents a novel stimulus useful to study the role of Ca⁺⁺ in human basophil mediator release.