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 approximately equal to 15 min), temperature and Ca++ dependent (optimal at 37 degrees 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 (approximately equal to 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 microM) inhibited the release of histamine induced by MTX, whereas the dihydropyridine nifedipine (0.1-10 microM) 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.
D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008387:Marine Toxins / Q000494:pharmacology*; D035964:Oxocins; D013189:SRS-A / Q000378:metabolism*; D013696:Temperature; D000095702:Polyether Toxins
D002118:Calcium; D002121:Calcium Channel Blockers; D000242:Cyclic AMP; D007073:Immunoglobulin E; D008387:Marine Toxins; D035964:Oxocins; D013189:SRS-A; C020394:maitotoxin; D000095702:Polyether Toxins