title: Role of phospholipase A2 activation in histamine release from human basophils.
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.
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D001491:Basophils / Q000276:immunology / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008555:Melitten / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D008555:Melitten; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate; C006821:4-bromophenacyl bromide