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Expression and Functionality of Anti-Human Immunodeficiency Virus and Anticancer Drug Uptake Transporters in Immune Cells

2007; American Society for Pharmacology and Experimental Therapeutics; Volume: 324; Issue: 2 Linguagem: Inglês

10.1124/jpet.107.131482

1521-0103

Gerard Minuesa, Sergi Purcet, Itziar Erkizia, Mı́riam Molina-Arcas, Margarita Bofill, Nuria Izquierdo‐Useros, F. Javier Casado, Bonaventura Clotet, Marçal Pastor‐Anglada, Javier Martínez‐Picado,

Pharmacological Effects and Toxicity Studies

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.