Regulation of nucleoside transport by lipopolysaccharide, phorbol esters, and tumor necrosis factor-alpha in human B-lymphocytes.
Nucleoside transport systems and their regulation in human B-lymphocytes have been characterized using the cell lines Raji and Bare lymphoma syndrome-1 (BLS-1) as experimental models. These cells express at least three different nucleoside transport systems as follows: a nitrobenzylthioinosine-sensitive equilibrative transport system of the es-type, which appears to be associated with hENT1 expression, and two Na+-dependent transport systems that may correspond to N1 and to the recently characterized N5-type, which is nitrobenzylthioinosine-sensitive and guanosine-preferring. B cell activators such as phorbol 12-myristate 13-acetate and lipopolysaccharide (LPS) up-regulate both concentrative transport systems but down-regulate the equilibrative es-type transporter, which correlates with lower hENT1 mRNA levels. These effects are dependent on protein kinase C activity. Phorbol 12-myristate 13-acetate and LPS also induce an increase in tumor necrosis factor-alpha (TNF-alpha) mRNA levels, which suggest that this cytokine may mediate some of the effects triggered by these agents, since addition of TNF-alpha alone can increase N1 and N5 transport activities by a mechanism that also depends on protein kinase C activation. Interestingly, TNF-alpha down-regulates es activity, but this effect cannot be abolished by inhibiting protein kinase C. This study reveals differential regulation of nucleoside transport systems following activation of human B-lymphocyte cell lines by agents of physiological relevance such as TNF-alpha and LPS. Moreover, it indicates that the recently characterized N5 transport system can also be regulated following B cell activation, which may be relevant to lymphocyte physiology and to the treatment of lymphocyte malignancies.
Departament de Fisiologia (Immunologia) and Fundació Pi i Sunyer, Campus de Bellvitge, Universitat de Barcelona, Diagonal 645, 08071 Barcelona, Spain.
C
C
Soler
A
A
Felipe
J F
JF
Mata
F J
FJ
Casado
A
A
Celada
M
M
Pastor-Anglada
D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D001692:Biological Transport; D017931:DNA Primers; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009705:Nucleosides / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017931:DNA Primers; D008070:Lipopolysaccharides; D009705:Nucleosides; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate