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 little affected by protein kinase C inhibitors. We investigated the effects of GTP[S] and the protein kinase C inhibitor AMG-C16 on dioctanoyl-sn-glycerol (DiC8)-activated migration of rabbit neutrophils and compared them with the effects on fMet-Leu-Phe-activated migration and random migration. GTP[S] did not inhibit DiC8-activated migration or random migration but inhibited fMet-Leu-Phe-activated migration. AMG-C16 gave a strong inhibition of DiC8-activated migration but had only a small effect on fMet-Leu-Phe-activated migration and random migration. When fMet-Leu-Phe and DiC8 were added together in suboptimal concentrations an additive effect was found. Pretreatment with the diacylglycerol kinase inhibitor R59022 enhanced random migration. The enhancement was completely inhibited by AMG-C16 and was unaffected by GTP[S]. These findings suggest that DiC8-activated migration and fMet-Leu-Phe-activated migration are controlled by different pathways.
Boonen
G J
GJ
Department of Medical Biochemistry, University of Leiden, The Netherlands.
de Koster
B M
BM
Elferink
J G
JG
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004075:Diglycerides / Q000494:pharmacology*; D005995:Glyceryl Ethers / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011744:Pyrimidinones / Q000494:pharmacology; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology
D004075:Diglycerides; D005995:Glyceryl Ethers; D010972:Platelet Activating Factor; D011744:Pyrimidinones; D013844:Thiazoles; C034883:guanosine 5'-O-(2-thiotriphosphate); C044295:1,2-dioctanoylglycerol; C059039:1-O-hexadecyl-2-O-methylglycerol; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009240:N-Formylmethionine Leucyl-Phenylalanine; C047505:R 59022; D011493:Protein Kinase C