TAILIEUCHUNG - Báo cáo Y học: Differential effects of arachidonoyl trifluoromethyl ketone on arachidonic acid release and lipid mediator biosynthesis by human neutrophils

The goal of this study was to determine the effects of a putative specific cytosolic phospholipase A2 inhibitor, arachidonyl trifluoromethyl ketone (AACOCF3), on arachidonic acid (AA) release and lipid mediator biosynthesis by ionophore-stimulated human neutrophils. Initial studies indicated that AACOCF3 at concentrations 0–10 lM did not affect AA release from neutrophils. In contrast, AACOCF3 potently inhibited leukotriene B4 formation by ionophore-stimulated neutrophils (IC50 lM). | Eur. J. Biochem. 269 3760-3770 2002 FEBS 2002 doi Differential effects of arachidonoyl trifluoromethyl ketone on arachidonic acid release and lipid mediator biosynthesis by human neutrophils Evidence for different arachidonate pools Alfred N. Fonteh Department of Internal Medicine Division of Pulmonary and Critical Care Medicine Wake Forest University School of Medicine Medical Center Boulevard Winston-Salem NC 27157 USA. The goal of this study was to determine the effects of a putative specific cytosolic phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone AACOCF3 on arachidonic acid AA release and lipid mediator biosynthesis by ionophore-stimulated human neutrophils. Initial studies indicated that AACOCF3 at concentrations 0-10 M did not affect AA release from neutrophils. In contrast AACOCF3 potently inhibited leukotriene B4 formation by ionophore-stimulated neutrophils IC50 M . Likewise AACOCF3 significantly inhibited the biosynthesis of platelet activating factor. In cell-free assay systems 10 M AACOCF3 inhibited 5-lipoxygenase and CoA-independent transacylase activities. 3H AA labeling studies indicated that the specific activities of cell-associated AA mimicked that of leukotriene B4 and PtdCho PtdIns while the specific activities of AA released into the supernatant fluid closely mimicked that of PtdEtn. Taken together these data argue for the existence of segregated pools of arachidonate in human neutrophils. One pool of AA is linked to lipid mediator biosynthesis while another pool provides free AA that is released from cells. Additionally the data suggest that AACOCF3 is also an inhibitor of CoA-independent transacylase and 5-lipoxygenase. Thus caution should be exercised in using AACOCL-Ị as an inhibitor of cytosolic phospholipase A2 in whole cell assays because of the complexity of AA metabolism. Keywords arachidonic acid lipid mediators neutrophils phospholipase A2 inhibitor. Phospholipases A2 PLA2 are .

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