ABC transporters in human lymphocytes: expression, activity and role, modulating factors and consequences for antiretroviral therapies.
BACKGROUND
ATP-binding cassette (ABC) transporters are a superfamily of efflux pumps that transport numerous compounds across cell membranes. These transporters are located in various human tissues including peripheral blood cells, in particular lymphocytes, and present a high variability of expression and activity. This variability may affect the intracellular concentrations and efficacy of drugs acting within lymphocytes, such as antiretroviral drugs.


METHODS
This review focuses on the current knowledge about the expression, activity, roles and variability of ABC drug transporters in human lymphocytes. The identified modulating factors and their impact on the intracellular pharmacokinetics and efficacy of antiretroviral drugs are also detailed.


RESULTS
Controversial data regarding the expression, activity and sources of variability of ABC transporters in lymphocytes are discussed. The modulating factors and their pharmacological consequences regarding antiretroviral therapies are also provided.


CONCLUSIONS
Numerous studies have reported conflicting results regarding the expression and activity of ABC drug transporters in lymphocytes. Despite these discrepancies, which may partly result from heterogeneous analytical methods, ABCC1 appears to have the highest expression in lymphocytes and may thus play a predominant role in the resistance to antiretroviral drugs, particularly to protease inhibitors.
Giraud
Carole
C
Groupe Hospitalier Cochin - Saint-Vincent-de-Paul, Assistance Publique - Hôpitaux de Paris, Centre de Recherche Clinique Paris Descartes, Site Hôpital Tarnier, 89 rue d'Assas, 75006 Paris, France. carole.giraud@cch.aphp.fr
Manceau
Sandra
S
Treluyer
Jean-Marc
JM
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D044966:Anti-Retroviral Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1