Anti-CD69 antibodies enhance phorbol-dependent glucose metabolism and Ca2+ levels in human thymocytes. Antagonist effect of cyclosporin A.
The human activation antigen CD69 is an early inducible surface glycoprotein acquired by T cells in the thymus at the stage of positive selection and during activation of mature lymphoid cells both in vivo and in vitro. We have studied the regulatory influence of CD69 activation pathway on the glycolytic process and transduction signals of thymocytes. Treatment of human thymocytes with different anti-CD69 monoclonal antibodies (mAbs), in the presence of submitogenic doses of phorbol ester, produced an enhanced release of lactate without significant alterations in Fru 2,6-P2 levels or phosphofructokinase-2 (PFK-2) and pyruvate kinase activities. A small increase in phosphofructokinase-1 (PFK-1) activity was also detected. Furthermore, anti-CD69 mAb increased the glucose detritiation from [2-3H] and [3-3H]glucose, thus indicating an enhanced flux through hexokinase and PFK-1 steps. In addition, de novo synthesis of diacylglycerol and intracellular Ca2+ levels increased after anti-CD69 mAb treatment. The stimulatory effects of anti-CD69 mAb on both glycolysis and Ca2+ levels were inhibited by cyclosporin A. Because CD69 molecules are present in certain subset populations of immature thymocytes, the ability of anti-CD69 mAb to stimulate the glycolysis, the synthesis of diacylglycerol and the intracellular Ca2+ levels suggest that the activation signals delivered through CD69 molecules could play a role in the thymus cells maturation.
Conde
M
M
Departamento de Bioquimica Medica y Biologia Molecular, Facultad de Medicina, Universidad de Sevilla, Spain.
Montaño
R
R
Moreno-Aurioles
V R
VR
Ramirez
R
R
Sanchez-Mateos
P
P
Sanchez-Madrid
F
F
Sobrino
F
F
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D004075:Diglycerides / Q000096:biosynthesis; D004347:Drug Interactions; D005635:Fructosediphosphates / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D037181:Lectins, C-Type; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D016572:Cyclosporine; D004075:Diglycerides; D005635:Fructosediphosphates; D005947:Glucose; D007166:Immunosuppressive Agents; D007773:Lactates; D019344:Lactic Acid; D037181:Lectins, C-Type; D011773:Pyruvates; D019289:Pyruvic Acid; D013755:Tetradecanoylphorbol Acetate; D014316:Tritium; D000099192:CD69 Antigens; C027652:fructose 2,6-diphosphate