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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 28, 2008 Accepted June 22, 2008 A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration Rieneke van de Ven, George L Scheffer, Anneke W Reurs, Jelle J Lindenberg, Ruud Oerlemans, Gerrit Jansen, Jean-Pierre Gillet, Joel N Glasgow, Alexander Pereboev, David T Curiel, Rik J Scheper, and Tanja D de Gruijl* Department of Pathology, VU University Medical Center, Amsterdam, Netherlands Department of Medical Oncology, VU University Medical Center, Amsterdam, Netherlands Department of Rheumatology, VU University Medical Center, Amsterdam, Netherlands Department of Biology, University of Namur, Namur, Belgium Division of Cardiology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States Division of Human Gene Therapy (DHGT), University of Alabama at Birmingham, Birmingham, Alabama, United States * Corresponding author; email: td.degruijl{at}vumc.nl. The capacity of dendritic cells (DC) to migrate from peripheral organs to lymph nodes (LN) is important in the initiation of a T cell-mediated immune response. Previously it was shown that the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the multidrug resistance protein 1 (MRP1; ABCC1) 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 DC and contributes to the migratory capacity of DC. Pharmacological inhibition of MRP4 activity or down-regulation through RNAi in DC resulted in reduced migration of DC 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 PGE2, 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 towards the draining lymph nodes, and thereby 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: R. van de Ven, R. Oerlemans, J. W. van der Heijden, G. L. Scheffer, T. D. de Gruijl, G. Jansen, and R. J. Scheper ABC drug transporters and immunity: novel therapeutic targets in autoimmunity and cancer J. Leukoc. Biol., November 1, 2009; 86(5): 1075 - 1087. [Abstract] [Full Text] [PDF] 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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