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, Ellen S. Vitetta

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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CD19 and P-gp, rapidly resulting in the translocation of P-gp into a compartment on the plasma membrane where it is no longer active.

Original languageEnglish (US)
Pages (from-to)178-183
Number of pages6
JournalBlood
Volume104
Issue number1
DOIs
StatePublished - Jul 1 2004

Fingerprint

P-Glycoprotein
Anti-Idiotypic Antibodies
Lymphoma
Cells
Lipids
Cell Line
Antibodies
Pumps
Fluorescence Resonance Energy Transfer
Cell membranes
Epitopes
Cholesterol
Monoclonal Antibodies
Cell Membrane
Molecules

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Ghetie, Maria Ana; Marches, Radu; Kufert, Stephanie; Vitetta, Ellen S.

In: Blood, Vol. 104, No. 1, 01.07.2004, p. 178-183.

Research output: Contribution to journalArticle

@article{767336bd17174b39bddf664af8a8a350,
title = "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",
abstract = "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.",
author = "Ghetie, {Maria Ana} and Radu Marches and Stephanie Kufert and Vitetta, {Ellen S.}",
year = "2004",
month = "7",
day = "1",
doi = "10.1182/blood-2003-12-4255",
language = "English (US)",
volume = "104",
pages = "178--183",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

TY - JOUR

T1 - 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

AU - Ghetie, Maria Ana

AU - Marches, Radu

AU - Kufert, Stephanie

AU - Vitetta, Ellen S.

PY - 2004/7/1

Y1 - 2004/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=3042799345&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042799345&partnerID=8YFLogxK

U2 - 10.1182/blood-2003-12-4255

DO - 10.1182/blood-2003-12-4255

M3 - Article

C2 - 15001473

AN - SCOPUS:3042799345

VL - 104

SP - 178

EP - 183

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -