Cyclic AMP as a mediator of prostaglandin E-induced suppression of human natural killer cell activity

The role of cyclic AMP in mediating the prostaglandin (PG) E2-induced suppression of natural killer (NK) cell function was studied. Highly purified preparations of human large granular lymphocytes (LGL; which have been shown to be closely associated with human NK activity) and T lymphocytes were obtained by using Percoll gradients. Basal cyclic AMP was similar in both cell populations. With LGL, PGE2 (but not PGF2 alpha) suppressed NK activity (75%) and enhanced cellular cycle AMP (600%). In contrast, in small, high density T lymphocytes, PGE2 caused very small increases in cyclic AMP (20%). Phosphodiesterase inhibitors (PDEI) such as isobutyl methylxanthine and theophylline also increased cyclic AMP and suppressed NK activity in LGL. The effect of PGE2 and PDEI, in combination on cellular cyclic AMP and NK activity, was greater than the effect of each agent alone. Finally, exogenous derivatives of cyclic AMP also suppressed NK activity. These results indicate that in LGL, increased cellular cyclic AMP mediates the action of PGE2 on the suppression of NK activity.