INHIBITION OF PHORBOL ESTER-STIMULATED CHEMI-LUMINESCENCE IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES BY RETINOIC ACID AND 5,6-EPOXYRETINOIC ACID

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (1) , 216-222
Abstract
Chemiluminescence (CL) is an index of the generation of and reactions mediated by .**GRAPHIC**. and 1O2. The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), is a potent stimualtor of CL by human polymorphonuclear leukocytes; treatment with TPA (100 ng/ml) provokes a CL response that peaks within 5 min and persists for > 30 min. The response is proportional to concentration over the range of 10-100 ng/ml. The ability of different phorbol diesters to stimulate CL and .**GRAPHIC**. production correlates with their relative activities as tumor promoters in vivo. Non-phorbol diester tumor promoters such as iodoacetic acid, anthralin and Tween 60 are inactive in this system. The TPA-mediated stimulation of CL can be inhibited by retinoids; cells preincubated for 15 min with 100 .mu.M retinoic acid show only a marginal CL response to TPA. Addition of retinoic acid to resting polymorphonuclear leukocytes results in a transient burst of CL without concomitant .**GRAPHIC**. release, observations indicative of an excitable substrate. A similar CL response is seen when retinoic acid is incubated with potassium superoxide in a cell-free system. 5,6-Expoxyretinoic acid, an even more effective inhibitor of TPA-stimulated CL than retinoic acid when added simultaneously with TPA, does not undergo these 2 CL reactions. Retinoic acid may undergo oxidative activation to a species that can exert enhanced antipromoter activities. Polymorphonuclear leukocytes provide a useful system for exploring the roles of reactive oxygen species in the action mechanism of TPA and retinoic acid.