ACTIVATION OF NEUTROPHIL MIGRATION BY DIOCTANOYL-SN-GLYCEROL AND FMET-LEU-PHE IS CONTROLLED BY DIFFERENT PATHWAYS

Migration activated by fMet-Leu-Phe is inhibited by GTP[S] and is litt le affected by protein kinase C inhibitors. We investigated the effect s of GTP[S] and the protein kinase C inhibitor AMG-C-16 on dioctanoyl- sn-glycerol (DiC8)-activated migration of rabbit neutrophils and compa red them with the effects on fMet-Leu-Phe-activated migration and rand om migration. GTP[S] did not inhibit DiC8-activated migration or rando m migration but inhibited fMet-Leu-Phe-activated migration. AMG-C-16 g ave a strong inhibition of DiC8-activated migration but had only a sma ll effect on fMet-Leu-Phe-activated migration and random migration. Wh en fMet-Leu-Phe and DiC8 were added together in suboptimal concentrati ons an additive effect was found. Pretreatment with the diacylglycerol kinase inhibitor R59022 enhanced random migration. The enhancement wa s completely inhibited by AMG-C-16 and was unaffected by GTP[S]. These findings suggest that DiC8-activated migration and fMet-Leu-Phe-activ ated migration are controlled by different pathways.