title: Expressions of multidrug resistance protein 1 and multidrug resistance-associated protein 1 in lung dendritic cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We purified LDCs comprising ~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.
  
  
  RESULTS
  MDR1 blockade by the specific inhibitor verapamil reduced the percentage of rhodamine 123(low) cells in LDCs (from 31.8±6.3% 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shibata
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D014700:Verapamil; C421109:multidrug resistance-associated protein 1