Chemokinetic activity of N-formyl-methionyl-leucyl-phenylalanine on human neutrophils, and its modulation by phenylbutazone.
Phenylbutazone (PBZ) is known to inhibit the oriented migration of human polymorphonuclear leukocytes (PMNs) induced by formyl-methionyl-leucyl-phenylalanine (FMLP), and to protect these cells against the deactivation caused by their prior incubation with FMLP. To gain insight into the mechanism of these effects, we measured the oriented PMN migration under agarose induced, in the presence and absence of PBZ, by FMLP, zymosan-activated serum and Klebsiella pneumoniae culture supernatant. The two components of this migration, i.e. the speed (chemokinesis), and direction of locomotion (chemotaxis), were also assessed. At concentrations ranging from 10(-8) to 10(-5) M, FMLP displayed similar chemotactic activity but the speed of PMN locomotion was maximal for 10(-7) M, and lower for concentrations above and below this level. Oriented migration was proportional to the mean cell locomotion speed during the experiments. PBZ inhibited both the oriented migration and locomotion speed induced by 10(-7) M FMLP, but did not affect its chemotactic activity. At concentrations of 10(-6) and 10(-5) M, PBZ increased oriented migration and locomotion speed, again without influencing FMLP chemotactic activity. Oriented migration induced by zymosan-activated serum was not affected by PBZ but the migration induced by Klebsiella pneumoniae culture supernatant diminished slightly. These results demonstrate that PBZ modulates the chemokinetic effect of FMLP on PMNs and thus alters oriented PMN migration.
D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008715:Methionine / Q000031:analogs & derivatives*; D009239:N-Formylmethionine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010653:Phenylbutazone / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D009842:Oligopeptides; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D008715:Methionine; D010653:Phenylbutazone