title: Early increase in lymphocyte cyclic nucleotide phosphodiesterase activity upon mitogenic activation of human peripheral blood mononuclear cells.
abstract: Cyclic nucleotide phosphodiesterase activity of human peripheral blood mononuclear cells was significantly increased following a short (30 min) incubation with the mitogenic lectin Concanavalin A. Con A stimulated phosphodiesterase activity to the same extent whatever the subcellular compartment (homogenate, cytosol or pellet). Further separation of the Con A-activated mononuclear cells into lymphocyte-enriched and monocyte-enriched populations showed that the Con A-induced increase of phosphodiesterase activity exclusively affected the lymphocyte-enriched population. In lymphocytes, cyclic GMP phosphodiesterase activity was more importantly enhanced by Con A (+275%) than cyclic AMP phosphodiesterase activity (+75%). The increase of both activities occurred as early as from 10 min of Con A incubation and proved to be maximal with Con A doses of 2.5 and 5 micrograms per 10(6) cells, lower and higher doses being less effective. Inhibition experiments with reference inhibitors suggested that, among the high affinity phosphodiesterase isoforms, the cyclic GMP-inhibited enzyme might be more selectively enhanced by Con A than the cyclic AMP-specific, Rolipram-sensitive one. The non-mitogenic lectin Helix pomatia hemagglutinin, was not able to enhance cyclic nucleotide phosphodiesterase activity of human mononuclear cells whereas anti-CD3 monoclonal antibody, although being less effective than Con A, exhibited a significant stimulatory effect. Putting together these results suggest that the early increase in phosphodiesterase activity might be a normal step involved in the mitogenic activation of human lymphocyte.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U 205, Institut National des Sciences Appliquées de Lyon, Villeurbanne, France.
authors.forename: N
authors.initials: N
authors.lastname: Meskini
authors.forename: M
authors.initials: M
authors.lastname: Hosni
authors.forename: G
authors.initials: G
authors.lastname: Nemoz
authors.forename: M
authors.initials: M
authors.lastname: Lagarde
authors.forename: A F
authors.initials: AF
authors.lastname: Prigent
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000704:Analysis of Variance; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D037102:Lectins; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000201:enzymology; D011760:Pyrrolidinones / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020889:Rolipram
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; C038095:Helix lectin; D037102:Lectins; D011760:Pyrrolidinones; D011948:Receptors, Antigen, T-Cell; D003208:Concanavalin A; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP; D020889:Rolipram