CHEMOTACTIC DEACTIVATION OF HUMAN-NEUTROPHILS - PROTECTIVE INFLUENCE OF PHENYLBUTAZONE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 58  (4) , 752-758
Abstract
The antiinflammatory drug, phenylbutazone (PBZ), was 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 involved 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 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 provide an additional example of a compound outside of the N-formyl peptide series that interacts with the peptide receptor.