POSSIBLE ROLE OF PHOSPHOLIPASE-A2 IN TRIGGERING HISTAMINE-SECRETION FROM HUMAN BASOPHILS INVITRO

The possibility that phospholipase A2 (PLA2) activation plays a role in immediate hypersensitivity reactions was investigated. Two agents, p-bromophenacyl bromide (BPB) and mepacrine, which inhibit PLA2 activity in several tissues, cause a dose-dependent inhibition of histamine release from human basophils induced by several immunologic (i.e., antigen and anti-IgE) and nonimmunologic (i.e., formyl-methionine-containing peptide [(f-met peptide)] and the Ca2+ ionophore, A23187 [calcimycin]) stimuli. The inhibitory effect of BPB on histamine release is irreversible and extremely rapid. BPB is inhibitory in the whole reaction and in the 1st and 2nd stage of antigen- and anti-IgE-induced histamine release. Increasing the Ca2+ concentrations in the extracellular medium partially blocks the inhibitory effect of BPB. BPB is not a competitive antagonist of the effect of Ca2+, suggesting that the 2 agents act on distinct enzymatic sites. The inhibitory effect of BPB in the presence of exogenous arachidonic acid (AA) was less marked than in the absence of AA. The activation of cell surface receptors and/or the intracellular translocation of Ca2+ by the ionophore A23187 activates a basophil PLA2 which plays an essential role in the control of the release of preformed mediators.