Multidrug resistance protein (MRP) activity in normal mature leukocytes and CD34-positive hematopoietic cells from peripheral blood

Multidrug resistance proteins (MRPs) such as MRP1, MRP2 and MRP3 are membra ne efflux pumps involved in multidrug resistance and handling organic anion s. In the present study, MRP activity was investigated in normal mature leu cocytes and CD34-positive hematopoietic cells from peripheral blood using t he flow cytometric carboxy-2',7'-dichlorofluorsecein (CF) efflux assay. Bas al and similar cellular exports of CF, an anionic fluorescent dye substrate for MRP1 and MRP2 transporters, were evidenced in lymphocytes whatever the ir subsets (CD3, CD4, CD8, CD20 and CD56 cells), in CD14 monocytes and in C D15 granulocytes whereas higher CF efflux was found in CD34 cells. Such out wardly-directed transports of CF were inhibited by known blockers of MRP fu nction such as probenecid whereas the P-glycoprotein modulator verapamil di d not alter the retention of the dye in the blood leukocytes. Peripheral ma ture blood leukocytes were moreover found to express MRP1 mRNAs and MRP1 pr otein as assessed by Northern-blot and Western-blot analyses, whereas MRP2 and MRP3 transcripts were not present or only at very low levels. Mature le ukocytes therefore display basal constitutive MRP-related transport activit y regardless of cell lineage and likely related to MRP1 expression whereas higher MRP-related efflux can be detected in peripheral CD34 hematopoietic cells. (C) 2001 Elsevier Science Inc. All rights reserved.