title: Cyclic AMP-mediated alteration of the CD2 activation process in human T lymphocytes. Preferential inhibition of the phosphoinositide cycle-related transduction pathway.
abstract: Activation of human T lymphocytes via the CD2 molecule produces an enhanced turnover of phosphatidylinositol (PI) cycle-related phospholipids accompanied by the increased production of diacylglycerol (DG) and phosphorylated derivatives of inositol (IP). In this report we demonstrate that increased levels of intracellular cyclic AMP induced in human T lymphocytes by prostaglandin E2 or dibutyryl cAMP antagonize these early biochemical events of the CD2 activation process. Thus, a substantial inhibition of the CD2-induced increase in 32P-phosphatidic acid and 32P-PI values is observed. In parallel, both the DG production and the IP release triggered by the CD2 signal are strongly reduced contrasting with an almost conserved Ca2+ response. We also report here that cAMP does inhibit the CD2-induced proliferation in a dose-dependent manner while the proliferation generated independently of DG and IP production by a combination of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate is not affected. These results therefore suggest that (a) intracellular cAMP levels may participate in the regulation of the PI cycle-related transduction pathway involved in the activation process of human T lymphocytes via the CD2 molecule; (b) the observed cAMP-mediated functional inhibitory effects are mainly related to an alteration of this cellular transduction signal; and (c) considering the putative critical second messenger role in the T cell proliferative response of DG and IP, respectively thought to activate the protein kinase C and to raise the intracellular free Ca2+, the lowering of DG production may be the key event responsible for this cAMP-mediated effect.
mesh_terms: D000262:Adenylyl Cyclases / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D003994:Bucladesine / Q000494:pharmacology; D018801:CD2 Antigens; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004075:Diglycerides / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D010716:Phosphatidylinositols / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D004075:Diglycerides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011971:Receptors, Immunologic; D000001:Calcimycin; D003994:Bucladesine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium