Expressions of multidrug resistance protein 1 and multidrug resistance-associated protein 1 in lung dendritic cells

Aim: Multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) are ATP-binding cassette transporters that mediate the efflux of a broad spectrum of substances and xenobiotics from cells in barrier organs. Interestingly, they are expressed in immune cells including some kinds of dendritic cells (DCs). In the present study, the expressions and activities of MDR1 and MRP1 in mouse lung DCs (LDCs) were investigated. Main methods: We purified LDCs comprising similar to 98% MHC-Class II(+)/CD11c(+) cells using magnetic and flow cytometric cell sorting. The highly purified LDCs expressed MDR1 and MRP1 at both the mRNA and protein levels. The fluorescent probes rhodamine 123 and Fluo-3 were used as substrates in efflux assays to measure the transport activities of MDR1 and MRP1, respectively. Key findings: MDR1 blockade by the specific inhibitor verapamil reduced the percentage of rhodamine 123(low) cells in LDCs (from 31.8 +/- 63% to 11.8 +/- 2.8%, p<0.02). MRP1 blockade by the specific inhibitor MK-571 reduced the percentage of Fluo-3(low) cells in LDCs (from 53.8 +/- 1.7% to 26.8 +/- 6.4%, p<0.03). Significance: These data showed that LDCs exhibited MDR1- and MRP1-mediated efflux activities. MDR1 and MRP1 in LDCs may be involved in protective functions through their efflux activities. (C) 2011 Elsevier Inc. All rights reserved.