Nitric oxide regulates nucleoside transport in activated B lymphocytes.
Activation of human B lymphocytes by lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) results in the differential regulation of nucleoside uptake [Soler, C., Felipe, A., Mata, J. F., Casado, F. J., Celada, A., Pastor-Anglada, M. (1998) J. Biol. Chem. 273, 26939-26945]. Because nitric oxide (NO) is involved in the modulation of the apoptotic response of B cells, the effects of NO on the regulatory responses of these transport systems to phorbol esters has been studied in Raji cells by a combination of approaches that involve arginine depletion, inhibition of nitric oxide synthase, and non-enzymatic production of NO using a donor. Human B lymphocytes express three transport systems involved in nucleoside uptake: N1 and N5, which are concentrative and Na+-dependent, and the nitrobenzylthioinosine-sensitive equilibrative system es. Raji cells do not express significant amounts of iNOS mRNA or protein; thus, NO production is presumably constitutive. The data are consistent with a role of NO in maintaining the basal transport activities of the three systems: N1, N5, and es. However, the up-regulatory effect of PMA on N1 and N5 does not require NO, whereas the inhibition of es transport activity does. In summary, NO differentially modulates nucleoside transport systems in activated human B lymphocytes and thus, NO may also be involved in the regulation of nucleoside (i.e., adenosine) disposal by activated B cells.
Soler
C
C
Departament de Fisiologia (Immunologia) and Fundació Pi i Sunyer, Universitat de Barcelona, Spain.
Felipe
A
A
Casado
F J
FJ
Celada
A
A
Pastor-Anglada
M
M
D001120:Arginine / Q000037:antagonists & inhibitors / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D033721:Equilibrative Nucleoside Transporter 1; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008239:Lysine / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism / Q000494:pharmacology; D033703:Nucleoside Transport Proteins; D009705:Nucleosides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002352:Carrier Proteins; D033721:Equilibrative Nucleoside Transporter 1; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D033703:Nucleoside Transport Proteins; D009705:Nucleosides; D012333:RNA, Messenger; C498476:SLC29A1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D008239:Lysine; D013755:Tetradecanoylphorbol Acetate