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 Langhera ns 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 mu ltidrug resistance-associated protein (MRP), another ABC efflux pump sharin g numerous substrates with P-gp, in human monocyte-derived DC. Immunolabeli ng experiments and dye efflux assays indicated that such cells displayed el evated 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 t o 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 contra st to that of MRP, functional expression of P-gp was not detected in monocy te-derived DC. Such antigen presenting cells that constitute a promising to ot for antitumor vaccinal therapy therefore display differential expression of the efflux pumps P-gp and MRP. (C) American Society for Histocompatibil ity and Immunogenetics, 2001. Published by Elsevier Science Inc.