Document Detail


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.
MedLine Citation:
PMID:  15001473     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (ie, 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CD19 and P-gp, rapidly resulting in the translocation of P-gp into a compartment on the plasma membrane where it is no longer active.
Authors:
Maria-Ana Ghetie; Radu Marches; Stephanie Kufert; Ellen S Vitetta
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-03-04
Journal Detail:
Title:  Blood     Volume:  104     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-21     Completed Date:  2004-08-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  178-83     Citation Subset:  AIM; IM    
Affiliation:
Cancer Immunobiology Center, University of Texas Southwestern Medical Center at Dallas, 75390, USA.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / immunology,  metabolism,  pharmacology*
Antigens, CD19 / immunology*,  metabolism*
Burkitt Lymphoma / drug therapy,  metabolism*
Cell Line, Tumor
Cell Membrane / metabolism
Cell Survival / drug effects,  immunology
Drug Resistance, Multiple*
Drug Resistance, Neoplasm
G(M1) Ganglioside / metabolism
Gene Expression
Humans
Membrane Microdomains / metabolism*
P-Glycoprotein / antagonists & inhibitors,  metabolism*
Protein Binding
Protein Transport
Rhodamine 123 / metabolism
Grant Support
ID/Acronym/Agency:
CA-64679/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD19; 0/P-Glycoprotein; 37758-47-7/G(M1) Ganglioside; 62669-70-9/Rhodamine 123

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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