E.: Receptor-coupled signal transduction in human polymor phonuclear neutrophils: Effects of a novel inhibitor of phospholipase C-de pendant processes on cell responsiveness

1-[6-[[l 73-3-Methoxyestra-l,3,5(l O)-trien-l 7-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-731 22), an inhibitor of phospholipase C (PLC)-dependent processes in human platelets, was found to be a potent inhibitor of human polymorphonuclear neutrophil (PMN) activation by structurally unrelated receptor-specific agonists. U-731 22 caused a time- and concentration-dependent (0.1-1 zM) inhibition of myeloperoxidase and vitamin B12-binding protein release from PMNs exposed to N-formyl-methionyl-leucyl-phen-ylalanine, recombinant human C5a, leukotnene B4 and platelet-activating factor. Activation of the respiratory burst, as measured by superoxide anion production, in PMNs stimulated with these agonists was also suppressed by U-731 22. These data sug-gested that U-731 22 inhibited a component of signal transduction that was common to the mechanisms of action of these stimuli