title: Inhibition of human NK cell cytotoxicity by induction of cyclic AMP depends on impaired target cell recognition.
abstract: Induction of cyclic AMP (cAMP) depresses natural killer (NK) cell activity. The present results demonstrate that this is dependent on a decreased capacity of the effector cells to conjugate to target cells. This was found either if dibutyryl-cAMP was used or if cAMP was induced by adenylate cyclase stimulation with prostaglandin E1 (PGE1) or by inhibition of phosphodiesterase activity with the inhibitor ZK 62711. The sites of action for cAMP-induced NK suppression and interferon (IFN)-induced NK enhancement are demonstrated to be distinct, since IFN acts by increasing the lytic efficiency and the recycling capacity without influencing target binding. Sequential treatment with cAMP/IFN and IFN/cAMP shows that IFN can neither restore target binding when added after cAMP nor protect against the cAMP-induced target binding inhibition when added before cAMP. The results are discussed in view of earlier data on cAMP in relation to cell membrane functions and cellular recognition, the mechanism underlying the cAMP-induced target binding inhibition, and the potential of the NK system as an indicator for immunosuppression. The present work also demonstrates the particular subpopulation in peripheral blood which mediates most NK activity, to respond strongly to PGE1 stimulation with regard to cAMP induction.
mesh_terms: D000527:Alprostadil; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects*; D008214:Lymphocytes / Q000145:classification; D011458:Prostaglandins E / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram
chemical_list: D011458:Prostaglandins E; D011760:Pyrrolidinones; D003994:Bucladesine; D007372:Interferons; D000242:Cyclic AMP; D000527:Alprostadil; D020889:Rolipram