EVIDENCE FOR LIPOXYGENASE ACTIVITY IN INDUCTION OF HISTAMINE-RELEASE FROM RAT PERITONEAL MAST-CELLS BY CHELATED IRON

  • 1 January 1983
    • journal article
    • research article
    • Vol. 49  (1) , 1-8
Abstract
The Fe3+-deferrioxamine B chelate effectively induced histamine release from rat peritoneal mass cells. The release was maximum at exogenous Fe3+ concentrations of 10-100 .mu.M, and the chelate was nontoxic, as determined by trypan blue uptake. In many aspects the chelate-induced histamine release paralleled IgE-mediated release. The kinetics, temperature and Ca2+ dependence resembled antigen-induced release. Phosphatidylserine potentiated the release in Wistar rats but not in fawn-hooded rats, a strain which does not respond to phosphatidylserine potentiation. The chelate-induced histamine release was blocked by the metabolic inhibitors dinitrophenol, KCN, 2-deoxyglucose and antimycin A. Lipoxygenase inhibitors also effectively blocked release, indicating an involvement of fatty acid metabolism via the lipoxygenase pathway. Free radical scavengers and antioxidants antagonistic to lipid peroxidation also inhibited the chelate-induced histamine release. Endogenous cellular Fe may be involved in the generation of free radicals and lipid peroxidation; these may be early events in IgE-mediated release of histamine.