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 journalArticlepeer-review

47 Scopus citations

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CD19 and P-gp, rapidly resulting in the translocation of P-gp into a compartment on the plasma membrane where it is no longer active.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

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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