Target-effector interaction in the natural killer cell system. IV. Modulation by cyclic nucleotides.
Dibutyryl cAMP (dB-cAMP) and the cAMP elevating agents, prostaglandin E1, theophylline, and histamine markedly suppressed NK cytolytic function in a dose- and rate-dependent manner. The inhibition was rapidly induced and persisted in the presence of the drugs. Separate pretreatment of targets and highly purified NK cells, isolated by a target binding and velocity sedimentation technique, revealed that PGE1 and dB-cAMP acted at the level of the effector cell in a short-term cytolytic assay. In contrast to the inhibitory effects of cAMP elevating agents, dB-cGMP and carbamylcholine caused a small but significant acceleration in the rate of lysis and could compete with inhibitory doses of dB-cAMP to reduce the level of suppression thereby suggesting that the cAMP-cGMP ratio might be important in NK-mediated lysis. Insulin had no effect on NK activity, whereas T cell-mediated cytolysis was augmented by insulin and cGMP if the effector cells were taken early after alloimmunization but not later. Neither cAMP- nor cGMP-elevating agents affected the frequency of NK-target cell conjugates. These results are compatible with the hypothesis that cyclic nucleotides may be involved in triggering the lytic event within NK cells.
D000818:Animals; D001665:Binding Sites; D002450:Cell Communication; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D007328:Insulin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008805:Mice, Inbred A; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009712:Nucleotides, Cyclic / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology
D007328:Insulin; D009712:Nucleotides, Cyclic; D000242:Cyclic AMP; D006152:Cyclic GMP