Early increase in lymphocyte cyclic nucleotide phosphodiesterase activity upon mitogenic activation of human peripheral blood mononuclear cells.
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.
Meskini
N
N
Institut National de la Santé et de la Recherche Médicale U 205, Institut National des Sciences Appliquées de Lyon, Villeurbanne, France.
Hosni
M
M
Nemoz
G
G
Lagarde
M
M
Prigent
A F
AF
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
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