POLYMORPHONUCLEAR LEUKOCYTES ACTIVATION - IN-VITRO MODULATION BY 6-METHOXY-2-NAPHTHYLACETIC ACID, THE MAJOR ACTIVE METABOLITE OF NABUMETONE

Reported here are the results of a study carried out in order to assess the possible influence of the major circulating active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, on some aspects of polymorphonuclear leukocytes activation. The action of 6-methoxy-2-naphthylacetic acid was tested on the following features of polymorphonuclear leukocytes activation: reactive oxygen species production in polymorphonuclear leukocytes stimulated with different agonists, reactive oxygen species production in polymorphonuclear leukocytes treated with pertussis toxin, NADPH-oxidase activity. The findings showed that 6-methoxy-2-naphthylacetic acid decreased reactive oxygen species production in polymorphonuclear leukocytes stimulated with N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, and opsonized zymosan, but failed to provoke a decrease of reactive oxygen species production when the cells were stimulated with calcium ionophore A23187. Moreover, 6-methoxy-2-naphthylacetic acid did not influence the transduction of the signal following the binding of stimuli to membrane receptors, and NADPH-oxidase activity. Finally, our findings showed that 6-methoxy-2-naphthyl acetic acid had no scavenger effect on reactive oxygen species production. © 1993 The Italian Pharmacological Society.