Differential expression of influx and efflux transport proteins in human antigen presenting cells.
Human macrophages (M Phi) express cytochrome P450 enzymes verifying their capacity to metabolize a variety of endogenous and exogenous substances. Here we analysed the mRNA and protein expression of transport proteins involved in the uptake or export of drugs, hormones and arachidonic acid metabolites in dendritic cells (DC) and M Phi compared to their precursors - blood monocytes - using cDNA microarray, RT-PCR, Western-blot and immunostaining techniques. The transport proteins studied included members of the solute carrier organic anion transporter family (SLCO) and the multidrug resistance associated proteins (MRP) 1-6 belonging to the ATP-binding cassette subfamily C (ABCC). We found that only mRNA for SLCO-2B1, -3A1, and -4A1 were present in monocytes, M Phi and DC. Most interestingly the expression of SLCO-2B1 was markedly enhanced in M Phi as compared to monocytes and DC. The presence of mRNA for ABCC1, 3, 4, 5 and 6 in all three cell types was demonstrated. On protein level ABCC1/MRP1 which has been identified as leukotriene C(4) transporter was found to be the most abundant transporter in M Phi and DC. Blocking the ABCC1/MRP1 activity with the specific inhibitor MK571 resulted in a phenotypic change in DC but not in M Phi. Our data show that human blood monocytes and monocyte derived M Phi as well as DC express a specific profile of transporters involved in uptake and export of exogenous molecules like allergens or drugs, but also of endogenous substances in particular of inflammatory lipid mediators like leukotrienes and prostaglandins.
Department of Dermatology, University Hospital RWTH Aachen, Aachen, Germany.
Claudia
C
Skazik
Ruth
R
Heise
Oznur
O
Bostanci
Nora
N
Paul
Bernd
B
Denecke
Sylvia
S
Joussen
Klaudia
K
Kiehl
Hans F
HF
Merk
Gabriele
G
Zwadlo-Klarwasser
Jens Malte
JM
Baron
D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D027361:Organic Anion Transporters / Q000378:metabolism*
D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters