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 nucle oside uptake [Soler, C., Felipe, A., Mata, J. F., Casado, F. J., Celada, A. , Pastor-Anglada, M. (1998) J. Biol. Chem. 273, 26939-26945]. Because nitri c oxide (NO) is involved in the modulation of the apoptotic response of B c ells, the effects of NO on the regulatory responses of these transport syst ems to phorbol esters has been studied in Raji cells by a combination of ap proaches that involve arginine depletion, inhibition of nitric oxide syntha se, and non-enzymatic production of NO using a donor. Human B lymphocytes e xpress three transport systems involved in nucleoside uptake: N1 and N5, wh ich are concentrative and Na+-dependent, and the nitrobenzylthioinosine-sen sitive equilibrative system es, Raji cells do not express significant amoun ts of iNOS mRNA or protein; thus, NO production is presumably constitutive. The data are consistent with a role of NO in maintaining the basal transpo rt activities of the three systems: N1, N5, and es, However, the up-regulat ory effect of PMA on N1 and N5 does not require NO, whereas the inhibition of es transport activity does. In summary, NO differentially modulates nucl eoside 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.