The 5-lipoxygenase products can modulate the synthesis of platelet-activating factor (alkyl-acetyl GPC) in Ca-ionophore A23187-stimulated rat peritoneal macrophages.

The effect of 5-lipoxygenase products of arachidonic acid on 14-C-alkyl-acetyl-glycero-phosphocholine (14C-alkyl-acetyl GPC) production in rat peritoneal macrophages was investigated, using macrophages prelabeled with N-methyl-14C-alkyl-lyso-glycero-phosphocholine (14C-alkyl-lyso GPC) (prelabeled macrophages). Bromophenacyl bromide (BPB: phospholipase A2 inhibitor), and AA861 (5-lipoxygenase inhibitor) suppressed the production of 14C-alkyl-acetyl GPC in the A23187-stimulated prelabeled macrophages in a dose-dependent manner. A23187-induced hydrolysis of 14C-alkyl-acyl-glycero-phosphocholine (14C-alkyl-acyl GPC) and formation of 14C-alkyl-lyso GPC were also reduced by BPB and AA861. However, indomethacin (IND: cyclo-oxygenase inhibitor) had no significant effect on 14C-alkyl-acetyl GPC production in the A23187-stimulated prelabeled macrophages. Exogenously supplied 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) reversed the inhibitory effect of AA861 on 14C-alkyl-acetyl GPC production in A23187-stimulated prelabeled macrophages. Reduced hydrolysis of 14C-alkyl-acyl GPC and formation of 14C-alkyl-lyso GPC in A23187-stimulated prelabeled macrophages, which were pretreated with AA861, were also reversed by the addition of 5-HPETE and 5-HETE. However, LTB4 had no such effects. 5-HPETE and 5-HETE augmented the stimulatory effect of A23187 on 14C-alkyl-acetyl GPC production in prelabeled macrophages, while they could not stimulate alkyl-acetyl GPC production in the absence of A23187. These results suggest that 5-lipoxygenase products, especially 5-HPETE and 5-HETE, may play an important role in alkyl-acetyl GPC production in rat peritoneal macrophages.