Influence of adenosine deaminase inhibition on the phosphoinositide turnover in the initial stages of human T cell activation.
An experimental model of adenosine deaminase deficiency was established on the human T cell line Jurkat by using 2'-deoxycoformycin, a strong specific inhibitor of the enzyme. When deoxyadenosine was added to the inhibited cells, the nucleotide profile was modified reproducing that found in lymphocytes from adenosine deaminase-deficient children. The metabolism of phosphoinositides, analyzed by either the release of [3H]inositol phosphates or the breakdown of 32P-prelabeled phosphatidyl inositides, was compared in normal and modified cells where dATP was accumulated. No modification in 32P labeling of phosphoinositides was detectable within the 32P-loading period. However, when the cells were stimulated by phytohemagglutinin or anti-CD3 monoclonal antibody, the phosphoinositide hydrolysis was strongly reduced in the dATP-containing lymphoblasts. This decrease was correlated with the intracellular dATP concentration.
Buc
H A
HA
Faculté de Médecine, Necker-Enfants Malades, INSERM U75, Paris, France.
Moncion
A
A
Hamet
M
M
Houllier
A M
AM
Thuilier
L
L
Perignon
J L
JL
D000243:Adenosine Deaminase / Q000172:deficiency; D058892:Adenosine Deaminase Inhibitors; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002460:Cell Line; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
D058892:Adenosine Deaminase Inhibitors; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003838:Deoxyadenine Nucleotides; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; C026600:2'-deoxyadenosine triphosphate