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 × 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 × 10⁻⁶ m, and 3.5 × 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 × 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.