Reversible membrane association of neutrophil 5-lipoxygenase is accompanied by retention of activity and a change in substrate specificity.

摘要: Ionophore activation of the human polymorphonuclear neutrophil results in eicosanoid synthesis and accumulation inactive 5-lipoxygenase a membrane compartment. We report here that inhibition self-inactivation ionophore-treated neutrophils with reversible inhibitor zileuton, active fraction. In zileuton plus cells, 77% specific activity cytosolic enzyme from resting cells was diverted to fraction compared 22% translocated when ionophore alone used activate neutrophils. Accumulation membrane-associated inhibited reversed by translocation MK-886. The two times more efficient production leukotriene A4 arachidonate-derived 5-hydroperoxyeicosatetraenoic acid than enzyme. Unlike enzyme, could metabolize 12(S)- 15(S)-hydroxyeicosatetraenoic 5(S),12(S)- 5(S),15(S)-dihydroxyeicosatetraenoic acid, respectively. ability hydroxy fatty acids dependent upon 5-lipoxygenase-activating protein association, but lost if eluted These studies reveal for first time significant quantities can be detected activated show association alter substrate specificity which is further evidence role metabolites.