Stimulation of arachidonic acid metabolism in the polymorphonuclear leukocyte by an N-formylated peptide. Comparison with ionophore A23187.
Inhibitors of arachidonic acid oxygenation can inhibit polymorphonuclear leukocyte lysosomal enzyme release, aggregation, and generation of activated oxygen species, as stimulated by N-formylated chemotactic peptides. Guinea Guinea pig peritoneal leukocytes were prelabeled with [3H]arachidonic acid, and 6-keto-prostaglandin F1 alpha, thromboxane B2, prostaglandin E2, prostaglandin F2 alpha, and 5-monohydroxyeicosatetraenoic acid were identified as products produced by these cells. Both Ionophore A23187 and the N-formylated peptide, N-formylmethionylphenylalanine, significantly stimulated release of these products, with the exception of a lack of effect of N-formylmethionylphenylalanine on 6-keto-prostaglandin F1 alpha. This metabolite was found to be produced by contaminating mononuclear cells unresponsive to N-formylmethionylphenylalanine stimulation when cell preparations purified to 96 leads to 99% polymorphonuclear cells were studied. The ability of N-formylmethionylphenylalanine to stimulate arachidonic acid metabolism of polymorphonuclear leukocytes was specifically antagonized by a competitive blocker of the formylated peptide receptor, t-butoxy-carbonyl-leucyl-phenylalanyl-leucyl-phenylalanine. The results indicate that metabolism of arachidonic acid induced by N-formylmethionylphneylalanine could play a role in the responses of polymorphonuclear leukocytes to this peptide.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008715:Methionine / Q000031:analogs & derivatives*; D009239:N-Formylmethionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000097:blood
D000900:Anti-Bacterial Agents; D001095:Arachidonic Acids; D004151:Dipeptides; D011453:Prostaglandins; C017330:N-formylmethionylphenylalanine; D000001:Calcimycin; D009239:N-Formylmethionine; D008715:Methionine