Effect of inhibitors of arachidonic acid metabolism upon IgE and non-IgE-mediated histamine release.

Inhibitors of arachidonic acid metabolism were tested for their ability to block histamine release from human basophils. Eighteen inhibitors of lipoxygenases, cyclo-oxygenases, prostaglandin isomerases and thromboxane synthetases were tested. Agents inhibitory to the activity of lipoxygenases were effective blockers of IgE and non-IgE-mediated histamine release; agents antagonistic to cyclo-oxygenases, isomerases and thromboxane synthetases were not. These findings indicate that a functioning lipoxygenase pathway is essential for basophil activation and secretion and that the cyclo-oxygenase, isomerase and thromboxane synthetase pathways are not. Compounds antagonistic to phospholipase A also block histamine release, as does the intracellular Ca2+ antagonist TMB-8. The data are consistent with the idea that mast-cell and basophil activation and secretion involve phospholipase A generation of arachidonic acid, which is metabolized via the lipoxygenase pathway.