[Induction of anti-leukemic immunity of dendritic cells derived from multidrug resistant leukemia K562/A02 cells with high expression of P-glycoprotein and sensitive K562 cells]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Dec;13(6):1018-22.
[Article in Chinese]

Abstract

This study was aimed to investigate and compare the anti-leukemic effect mediated by dendritic cells (DC) derived from multidrug resistant (MDR) leukemia K562/A02 cells with high expression of p-glycoprotein (P-gp) and sensitive K562 cells. Multidrug resistant K562/A02 cell line and sensitive K562 cell line from chronic myeloid leukemia (CML) were induced for differentiating to DC in complete RPMI 1640 culture medium supplemented with GM-CSF (1 000 U/ml), IL-4 (500 U/ml) and TNF-alpha (100 ng/ml) for 14 days. The morphologic features of DC were observed by means of optical microscopy and the phenotype of DC was detected by flow cytometry. T-cell stimulating activity was determined by allogeneic lymphocyte reaction (allo-MLR). Cytotoxic activity was measured by MTT assay. The results indicated that DC derived from K562/A02 cells and K562 cells similarly showed the typical morphology of dendritic cell and expressed the surface differentiation antigens and costimulatory molecules CD1a, CD83, HLA-DR, CD80 and CD86 of DC. In allo-MLR, K562/A02-DC had a higher capacity to induce lymphocyte proliferation, compared with K562-DC (P < 0.05). K562/A02-DC and K562-DC could similarly generate specific cytotoxic activity against K562/A02 cells or K562 cells respectively, but low reactivity against HL-60 cells. More importantly, the cytotoxic activity mediated by K562/A02-DC was stronger than that by K562-DC against K562/A02 cells or HL-60/VCR cells (P < 0.01, respectively). It is concluded that functional DC can be differentiated from multidrug resistant leukemia K562/A02 cells as well as sensitive K562 cells in the presence of GM-CSF, IL-4 and TNF-alpha. Especially, DC derived from K562/A02 cells can induced a p-glycoprotein specific anti-leukemic immunity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • Antigens, CD / analysis
  • Antigens, CD1 / analysis
  • B7-1 Antigen / analysis
  • B7-2 Antigen / analysis
  • CD83 Antigen
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cytotoxicity, Immunologic
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Immunoglobulins / analysis
  • Interleukin-4 / pharmacology
  • K562 Cells
  • Leukemia / immunology
  • Leukemia / pathology
  • Membrane Glycoproteins / analysis
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antigens, CD
  • Antigens, CD1
  • B7-1 Antigen
  • B7-2 Antigen
  • CD1a antigen
  • Immunoglobulins
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Doxorubicin
  • Granulocyte-Macrophage Colony-Stimulating Factor