Facilitation of cAMP increments during ADCC mediated by monocytes pretreated with cAMP-elevating agents

Abstract

Addition of IgG-sensitized human erythrocytes to peripheral blood monocytes elicit a transient increment in monocyte cAMP levels. This increase in cAMP was facilitated when monocytes were preincubated with the phosphodiesterase inhibitors, isobutylmethylxanthine (IBMX) and theophylline, and the adenylate cyclase agonists, isoproterenol and prostaglandin E1 (PGE1). Although these cAMP elevating agents were able to inhibit monocyte ADCC, the degree of inhibition could not be anticipated from the cAMP levels achieved by these drugs since theophylline inhibited monocyte ADCC in doses not elevating cAMP and PGE1, isoproterenol and IBMX were less effective inhibitors of monocyte ADCC than theophylline when comparing their effects on cAMP levels. Both PGE1-induced elevation of cAMP levels and the further increments of cAMP after addition of IgG-sensitized erythrocytes to PGE1-treated monocytes were significantly correlated to the inhibition of beta-glucuronidase release during ADCC. Theophylline in doses of 0.5 mM did not elevate basal levels of monocyte cAMP but facilitated the ADCC-induced cAMP increment concomitant with inhibition of monocyte ADCC and degranulation. Possibly, facilitation of cAMP increments during ADCC by an inhibitory feedback mechanism may be responsible for the inhibition caused by cAMP-elevating agents.