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.
- Author:
Yan-Ming ZHANG
1
;
Lian-Sheng ZHANG
;
Yu-Fang ZHANG
;
Liang-Cai YI
;
Ye CHAI
;
Fei-Xue SONG
;
Peng-Yun ZENG
;
Ying LIU
Author Information
1. Department of Hematology and Oncology, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
- Publication Type:Journal Article
- MeSH:
ATP-Binding Cassette, Sub-Family B, Member 1;
biosynthesis;
Antigens, CD;
analysis;
Antigens, CD1;
analysis;
B7-1 Antigen;
analysis;
B7-2 Antigen;
analysis;
Cell Differentiation;
drug effects;
immunology;
Cytotoxicity, Immunologic;
Dendritic Cells;
cytology;
immunology;
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;
pathology;
Membrane Glycoproteins;
analysis;
Tumor Necrosis Factor-alpha;
pharmacology
- From:
Journal of Experimental Hematology
2005;13(6):1018-1022
- CountryChina
- Language: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.