RETINOIDS INHIBIT THE RESPIRATORY BURST AND DEGRANULATION OF STIMULATED HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Retinoids exhibit a wide spectrum of activities, including antiinflammatory properties. We have investigated the effect of retinoic acid (RA) and retinyl acetate (RAc) on the production of reactive oxygen metabolites and the release of lysosomal enzymes by human polymorphonuclear leukocytes (PMN). Incubation of PMN with RAc or RA (1-100-mu-M) caused a dose-dependent inhibition (up to 90%) in O2-production and chemiluminescence induced by phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (fMLP), opsonized zymosan or ionophore A23187. Both retinoids (1-100-mu-M) also inhibited, in a dose-dependent way, degranulation induced by fMLP (up to 85% at the highest concentration of RA). These inhibitory effects appear irreversible, since they persist after the drugs are removed and the cells washed before stimulation. Inhibitors of cyclo-oxygenase activity such as acetyl-salicylic acid and indomethacin did not influence the effects of RAc. In contrast, BW755, an inhibitor of both cyclooxygenase and lipoxygenase, reversed the inhibitory action of RAc, suggesting that the effect of retinoids occurs possibly through the mediation of lipoxygenase products. The modulation of PMN oxidative metabolism and degranulation might help explain the antiinflammatory properties of retinoids.