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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2353-2359. Prepublished online as a Blood First Edition Paper on July 14, 2008; DOI 10.1182/blood-2008-03-147850. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-03-147850v1 112/6/2353    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by van de Ven, R. Articles by de Gruijl, T. D. Search for Related Content PubMed PubMed Citation Articles by van de Ven, R. Articles by de Gruijl, T. D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration Rieneke van de Ven1, George L. Scheffer1, Anneke W. Reurs1, Jelle J. Lindenberg2, Ruud Oerlemans3, Gerrit Jansen3, Jean-Pierre Gillet4, Joel N. Glasgow5,6, Alexander Pereboev5, David T. Curiel5, Rik J. Scheper1, and Tanja D. de Gruijl2 Departments of1 Pathology 2 Medical Oncology, and 3 Rheumatology, VU University Medical Center, Amsterdam, The Netherlands; 4 Department of Biology, University of Namur, Namur, Belgium; and Divisions of5 Human Gene Therapy and 6 Cardiology, Department of Medicine, University of Alabama at Birmingham The capacity of dendritic cells (DCs) to migrate from peripheral organs to lymph nodes (LNs) is important in the initiation of a T cell–mediated immune response. The ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the multidrug resistance protein 1 (MRP1; ABCC1) have been shown to play a role in both human and murine DC migration. Here we show that a more recently discovered family member, MRP4 (ABCC4), is expressed on both epidermal and dermal human skin DCs and contributes to the migratory capacity of DCs. Pharmacological inhibition of MRP4 activity or down-regulation through RNAi in DCs resulted in reduced migration of DCs from human skin explants and of in vitro generated Langerhans cells. The responsible MRP4 substrate remains to be identified as exogenous addition of MRP4's known substrates prostaglandin E2, leukotriene B4 and D4, or cyclic nucleotides (all previously implicated in DC migration) could not restore migration. This notwithstanding, our data show that MRP4 is an important protein, significantly contributing to human DC migration toward the draining lymph nodes, and therefore relevant for the initiation of an immune response and a possible target for immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Yoshioka, H. Sagara, F. Takahashi, N. Harada, K. Nishio, A. Mori, H. Ushio, K. Shimizu, T. Okada, M. Ota, et al. Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation Am J Physiol Lung Cell Mol Physiol, January 1, 2009; 296(1): L30 - L36. [Abstract] [Full Text] [PDF]

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