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Blood, 1 July 2004, Vol. 104, No. 1, pp. 178-183. Prepublished online as a Blood First Edition Paper on March 4, 2004; DOI 10.1182/blood-2003-12-4255. This Article Full Text (PDF) All Versions of this Article: 2003-12-4255v1 104/1/178    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 Ghetie, M.-A. Articles by Vitetta, E. S Search for Related Content PubMed PubMed Citation Articles by Ghetie, M.-A. Articles by Vitetta, E. S Social Bookmarking                   What's this? Submitted December 18, 2003 Accepted February 24, 2004 An anti-CD19 antibody inhibits the interaction between P-glycoprotein (P-gp) and CD19, causes P-gp to translocate out of lipid rafts, and chemosensitizes a multidrug-resistant (MDR) lymphoma cell line Maria-Ana Ghetie, Radu Marches, Stephanie Kufert, and Ellen S Vitetta* Cancer Immunobiology Center, UT Southwestern Medical Center, Dallas, TX, USA * Corresponding author; email: ellen.vitetta{at}utsouthwestern.edu. We have previously demonstrated that an anti-CD19 monoclonal antibody (MAb) (HD37) inhibits the function of the P-glycoprotein (P-gp) pump in a multidrug resistant (MDR) B-lymphoma cell line, Namalwa/MDR1, and that this effect is not due to the recognition of a cross-reactive epitope on P-gp. In this study, we have used the same cell line to define the mechanisms responsible for the effect of HD37 on the P-gp pump. Using fluorescence resonance energy transfer (FRET), we show that CD19 and P-gp are constitutively associated in cells. In the absence of treatment with anti-CD19, 40% of P-gp molecules expressed by Namalwa/MDR1 cells reside in the low-density lipid (i.e. cholesterol-rich) microdomains (lipid rafts). Following treatment of the cells with HD37 and disruption of the interactions between P-gp and CD19, P-gp translocated out of lipid rafts and CD19 translocated into lipid rafts. The effect of chemosensitization on Namalwa/MDR1 cells was specific for CD19; an anti-CD22 MAb had no such effect although the cells express CD22. These results suggest that anti-CD19 might chemosensitize P-gp+ cells by interfering with interactions between CD19 and P-gp, rapidly resulting in the translocation of P-gp into a compartment on the plasma membrane where it is no longer active. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. F. De Rosa, C. Ackerley, B. Wang, S. Ito, D. M. Clarke, and C. Lingwood Inhibition of Multidrug Resistance by AdamantylGb3, a Globotriaosylceramide Analog J. Biol. Chem., February 22, 2008; 283(8): 4501 - 4511. [Abstract] [Full Text] [PDF] C. H. Storch, R. Ehehalt, W. E. Haefeli, and J. Weiss Localization of the Human Breast Cancer Resistance Protein (BCRP/ABCG2) in Lipid Rafts/Caveolae and Modulation of Its Activity by Cholesterol in Vitro J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 257 - 264. [Abstract] [Full Text] [PDF] J. Troost, H. Lindenmaier, W. E. Haefeli, and J. Weiss Modulation of Cellular Cholesterol Alters P-Glycoprotein Activity in Multidrug-Resistant Cells Mol. Pharmacol., November 1, 2004; 66(5): 1332 - 1339. [Abstract] [Full Text] [PDF]

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