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(Journal of Leukocyte Biology. 2001;70:920-930.)
© 2001 by Society for Leukocyte Biology

Cytokines regulate membrane adenosine deaminase on human activated lymphocytes

Oscar J. Cordero*, Francisco J. Salgado*, Carmen M. Fernández-Alonso*, Carolina Herrera{dagger}, Carmen Lluis{dagger}, Rafael Franco{dagger} and Montserrat Nogueira*

* Departments of Biochemistry and Molecular Biology, University of Santiago de Compostela, 15706 Santiago de Compostela, and
{dagger} Departments of Biochemistry and Molecular Biology, University of Barcelona, 08108 Barcelona, Spain

Correspondence: Dr. Montserrat Nogueira Alvarez, Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela, Facultade de Bioloxía, Campus Sur., 15782 Santiago de Compostela, Galicia, Spain. E-mail: bnlmna{at}usc.es

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.

Key Words: ectoenzymes • protein translocation pathways • CD26 • interleukins • immunoregulatory mechanisms • Brefeldin A




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