Differential expression of the efflux pumps P-glycoprotein and multidrug resistance-associated protein in human monocyte-derived dendritic cells.
P-glycoprotein (P-gp), an ATP-binding cassette (ABC) drug efflux pump, has been recently shown to play an important role in the physiology of Langherans cells, a subtype of dendritic cells (DC) found in the skin. The present study was designed to investigate expression and activity of P-gp and of multidrug resistance-associated protein (MRP), another ABC efflux pump sharing numerous substrates with P-gp, in human monocyte-derived DC. Immunolabeling experiments and dye efflux assays indicated that such cells displayed elevated levels of MRP activity and expression when compared to those present in parental monocytes. Generation of DC from monocytes in the presence of the MRP inhibitor indomethacin did not, however, alter the capacity of DC to stimulate allogeneic T cells proliferation in mixed lymphocyte reaction. In addition, indomethacin did not inhibit the up-regulation of the CD1a, a marker occurring during the differentiation of monocytes into DC. In contrast to that of MRP, functional expression of P-gp was not detected in monocyte-derived DC. Such antigen presenting cells that constitute a promising tool for antitumor vaccinal therapy therefore display differential expression of the efflux pumps P-gp and MRP.
Laupèze
B
B
Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, Faculté de Médecine, UPRES EA 22-33, Rennes, France. blaupeze@yahoo.fr
Amiot
L
L
Bertho
N
N
Grosset
J M
JM
Lehne
G
G
Fauchet
R
R
Fardel
O
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000276:immunology*; D005452:Fluoresceins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D020014:K562 Cells; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005452:Fluoresceins; C053897:5(6)-carboxy-2',7'-dichlorofluorescein; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011339:Probenecid