High levels of P-glycoprotein activity in human lymphocytes in the first 6 months of life.
P-glycoprotein (P-gp) is an efflux transporter that controls the intracellular concentrations of drugs. Human development may modulate P-gp function. We investigated the effect of age on P-gp activity and MDR1 gene expression in lymphocytes. We also assessed the influence of human immunodeficiency virus (HIV) infection. We used 3,3'-diethyloxacarbocyanin iodide (DiOC(6)) efflux, estimated by flow cytometry, to quantify P-gp activity in 94 children (age range, 0-18 years) and 25 adults. MDR1 gene expression was quantified using reverse transcription-PCR (RT-PCR). In T and natural killer (NK) cell populations, P-gp activity peaked at birth, decreased between the ages of 0 and 6 months, and stabilized between the ages of 6 months and 2 years (P < 10(-6)). These maturation profiles were also strongly correlated (r = 0.67, P < 10(-6)). HIV infection did not affect P-gp activity in the lymphocytes of children. MDR1 gene expression was not influenced by age, nor was it correlated with P-gp activity. The high levels of P-gp activity observed in the lymphocytes of children ~6 months of age may affect the efficacy of intracellular drugs.
Giraud
C
C
Université Paris Descartes, Paris, France. carole.giraud@cch.aphp.fr
Declèves
X
X
Perrot
J Y
JY
Manceau
S
S
Pannier
E
E
Firtion
G
G
Morini
J P
JP
Chappuy
H
H
Batteux
F
F
Chouzenoux
S
S
Scherrmann
J M
JM
Blanche
S
S
Tréluyer
J M
JM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000097:blood*; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism*; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1