Abstract
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.
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