Effect of 15-Hydroxyeicosatetraenoic Acid (15-HETE) on Anti-Immunglobulin E- and Calcium Ionophore-Induced Histamine Release from Human Leukocytes

Abstract

15-Hydroxyeicosatetraenoic acid (15-HETE) was prepared by soybean lipoxygenase-mediated oxygenation of arachidonic acid to 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and subsequent reduction by NaBH4. 15-HETE was identified, purified and proved as biologically active by TLC, high pressure liquid chromatography, gas chromatography/mass spectrometry, and biological experiments on horse thrombocytes and rabbit peritoneal leukocytes. 15-HETE (0.1 to 0 .mu.M) was added to peripheral leukocytes of 48 human donors (33 atopics, 15 nonatopics) which were challenged with rabbit anti-human-IgE or Ca ionophore A 23187 [calcimycin]. Its effect was compared with the effects of nordihydroguaretic acid (NDGA) and eicosatetraenoic acid (ETYA). NDGA and ETYA markedly inhibited histamine release (17 .mu.M: 74 .+-. 11 and 39 .+-. 14.3%, respectively) while 15-HETE neither stimulated nor inhibited spontaneous anti-IgE- or A23187-induced histamine release.