Expression and functionality of anti-human immunodeficiency virus and anticancer drug uptake transporters in immune cells.
Almost all drugs used in anti-human immunodeficiency virus (HIV)-1 and anticancer therapies require membrane proteins to get into the cell to develop their proper activity. Nevertheless, little is known regarding the expression and activity of specific carriers involved in the uptake of these drugs in immune cells. Here, we assessed the mRNA levels, protein expression profile, and activity of the gene families SLC28 (coding for concentrative nucleoside transporters, hCNT1-3), SLC29 (equilibrative nucleoside transporters, hENT1-2), and SLC22 (organic cation transporters, hOCT1-3 and hOCTN1-2). Both hENTs and hCNT2 were abundant in primary lymphocytes, with a preferential activity of hENT1. A significant up-regulation in hENTs expression (100-fold) and activity (30-fold) was seen under stimulation of primary T lymphocytes. In contrast, monocytes, monocyte-derived macrophages (MDMs), and immature monocyte-derived dendritic cells predominantly expressed hCNT3, a functional transporter in MDMs. Finally, in immune cells, hOCTs showed a more heterogeneous expression profile and a lower activity than human nucleoside transporters (hNTs), although up-regulation of hOCTs also occurred upon lymphocyte activation. Overall, the expression and activity of most of the studied transporters emphasize their relevance in relation to anti-HIV and anticancer therapies. The identification of the transporter involved in each specific drug uptake in immune cells could help to optimize pharmacological therapeutic responses.
Minuesa
Gerard
G
IrsiCaixa Foundation, Hospital Germans Trias i Pujol, 08190 Badalona, Barcelona, Spain.
Purcet
Sergi
S
Erkizia
Itziar
I
Molina-Arcas
Míriam
M
Bofill
Margarita
M
Izquierdo-Useros
Nuria
N
Casado
F Javier
FJ
Clotet
Bonaventura
B
Pastor-Anglada
Marçal
M
Martinez-Picado
Javier
J
D019380:Anti-HIV Agents / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; D012333:RNA, Messenger