title: Cytokines regulate membrane adenosine deaminase on human activated lymphocytes.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.
authors.forename: O J
authors.initials: OJ
authors.lastname: Cordero
authors.forename: F J
authors.initials: FJ
authors.lastname: Salgado
authors.forename: C M
authors.initials: CM
authors.lastname: Fernández-Alonso
authors.forename: C
authors.initials: C
authors.lastname: Herrera
authors.forename: C
authors.initials: C
authors.lastname: Lluis
authors.forename: R
authors.initials: R
authors.lastname: Franco
authors.forename: M
authors.initials: M
authors.lastname: Nogueira
mesh_terms: 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
chemical_list: D016207:Cytokines; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase