Protective effect of indomethacin against chemotactic deactivation of human neutrophils induced by formylated peptide.
The effects of the nonsteroidal antiinflammatory drug indomethacin on the parameters relating to the migration and respiratory burst of human polymorphonuclear leukocytes (PMN) were studied in an attempt to clarify the mechanism of this drug's action on PMN. At various concentrations below 200 micrograms/ml, indomethacin partially inhibited the spontaneous migration of PMN but did not alter the directional migration induced by C5a-activated serum. In the presence of N-formyl-methionyl-leucyl-phenylalanine (FMLP) as chemoattractant, directed PMN migration was either inhibited or stimulated by indomethacin, depending on FMLP concentration. When PMN migration was induced by the optimal and suboptimal FMLP concentrations of 10(-7) and 10(-8) M, indomethacin inhibited this migration, but when the high FMLP concentration of 10(-6) M depressed this migration by chemotactic deactivation, indomethacin restored it to its maximum. Both the inhibitory and stimulatory effects of indomethacin on FMLP-induced PMN migration were due to changes in the migration speed. Indomethacin also inhibited FMLP-induced changes in the shape of floating PMN, and in respiratory burst, as well as specific FMLP binding to PMN. In contrast, indomethacin did not alter the PMN respiratory burst induced by phorbol myristate acetate or C5a-activated serum. These data show that indomethacin is able to prevent the loss of PMN chemokinetic activity induced by formylated peptides and suggest that it might be useful for investigating the mechanism of peptide-induced chemotactic deactivation.
Perianin
A
A
INSERM U. 294, Faculté de Médecine Xavier, Bichat, Paris, France.
Gaudry
M
M
Marquetty
C
C
Giroud
J P
JP
Hakim
J
J
D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007213:Indomethacin