Chemotactic deactivation of human neutrophils: protective influence of phenylbutazone.
The antiinflammatory drug, phenylbutazone (PBZ), has been studied in terms of its influence on chemotactic deactivation of human neutrophils. When PBZ was present during the time of preincubation of cells with N-formyl-methionyl-phenylalanine (F-Met-Phe), loss of subsequent spontaneous mobility and chemotactic responsivity to F-Met-Phe did not occur. The action of PBZ to protect neutrophils from peptide-mediated chemotactic deactivation was found to involve in part its inhibitory influence on hexose monophosphate shunt activity and in part its antagonistic effect on interaction of peptide receptors with N-formyl peptide. Phenylbutazone interfered with binding of N-formyl-methionyl-leucyl-[3H]phenylalanine but not [125I]C5a to the neutrophil, displaced labeled tripeptide bound in the absence of PBZ, increased the dissociation constant (KD) for labeled tripeptide, and limited down regulation of peptide receptor function. These results provide an example of drug-mediated modulation of the interaction of neutrophils with N-formyl peptide and strongly support the possibility that PBZ interacts directly and specifically with the human neutrophil peptide receptor as a competitive antagonist. They also provide an additional example of a compound outside of th N-formyl peptide series that interacts with the peptide receptor.
D000706:Anaphylatoxins / Q000378:metabolism; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000378:metabolism; D015936:Complement C5a; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils; D010653:Phenylbutazone / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D044042:Receptors, Formyl Peptide
D000706:Anaphylatoxins; D003182:Complement C5; D004151:Dipeptides; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D044042:Receptors, Formyl Peptide; C017330:N-formylmethionylphenylalanine; D009239:N-Formylmethionine; D015936:Complement C5a; D010653:Phenylbutazone