Role of phospholipase A2 activation in histamine release from human basophils

The present experiments were undertaken to investigate the role of phospholipase A2 (PLA2) activation in histamine release from human basophils. A PLA2 inhibitor, P-bromophenacyl bromide (BPB), inhibited IgE-mediated anti-IgE-induced histamine release from human basophils with a concentration of drug required to produce 50% inhibition (IC50) of 1.5 x 10(-6) M when leukocytes were preincubated with this agent for 15 min. Histamine release induced by calcium ionophore A23187 and formyl-L-methionyl-L-leucyl-L-phenylalanine was also blocked by BPB with IC50 of 4.1 x 10(-6) M, and 3.5 x 10(-6) M, respectively. A PLA2 activator, 12-0-tetradecanoylphorbol-13-acetate (TPA) caused basophil histamine release with a dose-dependent fashion. BPB inhibited TPA-induced histamine release (IC50: 2.5 x 10(-6) M). However, another PLA2 activator, melittin, and PLA2 did not release histamine through non-cytotoxic mechanisms. Collectively, these results suggest that PLA2 activation plays a central role in histamine release from human basophils via generation of lysophosphatidylcholine or products of the lipoxygenase pathway of arachidonic acid metabolism.