Cytokines regulate membrane adenosine deaminase on human activated lymphocytes.
CD26 is a lymphocyte marker that can anchor adenosine deaminase (ADA) on the T cell surface. We found that ADA is regulated by cytokines on the cell surface during T cell activation. By means of flow cytometry, immunofluorescence, and immunoblotting techniques, we found that interleukin (IL)-2 and IL-12 up-regulate ecto-ADA and CD26 expression. In clear contrast, IL-4 led to down-regulation of lymphocyte surface ADA without modifying the level of CD26. Moreover, neither circulating ADA transcription nor mRNA translation was regulated by cytokines. These results, along with absence of total-ADA modulation, the variable amount of ADA found in purified plasma membranes, and the different effect of Brefeldin A on the surface presence of ADA and CD26 indicated that cytokines regulate the translocation of ADA towards the cell surface through a mechanism not involving CD26. Ecto-ADA protected activated lymphocytes from the toxic effects of extracellular adenosine. Therefore, this cell surface ADA control might constitute part of the fine immunoregulatory mechanism of adenosine-mediated signaling through purinergic receptors in leukocytes.
Cordero
O J
OJ
Department of Biochemistry, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.
Salgado
F J
FJ
Fernández-Alonso
C M
CM
Herrera
C
C
Lluis
C
C
Franco
R
R
Nogueira
M
M
D000243:Adenosine Deaminase / Q000096:biosynthesis / Q000276:immunology*; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase