Influence of development, HIV infection, and antiretroviral therapies on the gene expression profiles of ABC transporters in human lymphocytes.
The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive, and antiretroviral drugs depends on their intracellular concentrations, which could be modulated by membrane efflux pumps belonging to the ABC transporter superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1, MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV-infected, respectively). Gene expression levels were quantified by quantitative RT-PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5 gene. BCRP and MRP4 genes were significantly higher expressed at birth than after 1 month of life. Neither HIV infection nor antiretroviral therapies modulated the gene expression profiles of ABC transporters. In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns.
Giraud
Carole
C
Centre de Recherche Clinique Paris Descartes, Groupe Hospitalier Cochin-Saint-Vincent-de-Paul, Assistance Publique-Hôpitaux de Paris, Site Hôpital Tarnier, 75006 Paris, France. carole.giraud@cch.aphp.fr
Manceau
Sandra
S
Declèves
Xavier
X
Goffinet
François
F
Morini
Jean-Pierre
JP
Chappuy
Hélène
H
Batteux
Frédéric
F
Chouzenoux
Sandrine
S
Yousif
Salah
S
Scherrmann
Jean-Michel
JM
Blanche
Stéphane
S
Tréluyer
Jean-Marc
JM
D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000378:metabolism*; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
D018528:ATP-Binding Cassette Transporters; D019380:Anti-HIV Agents; D015215:Zidovudine