Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor and interleukin 4 induce differentiation in the U-937 human monocytic leukemia cell line.
We studied the effect of TPA, G-CSF, GM-CSF, conditioned medium from 5637 cells (CM5637) and IL-4 on U-937 cell line proliferation and differentiation. Flow cytometry analysis showed that the expression of the CD14 cell surface antigen, initially detected in 90% of the cells, decreased when the cells were cultured with either G-CSF, GM-CSF, CM5637, or IL-4. The CD11c expression only decreased by exposure to GM-CSF and IL-4. The cells also showed a decrease in alpha-naphthylesterase (alpha-NAE) activity and an increase in peroxidase (Px) activity in the GM-CSF supplemented cultures. Remarkable changes in cell morphology were also observed. IL-4 induced morphologic features resembling histiocytic-like cells positive for the expression of alpha-NAE and negative for Px. GM-CSF induced cells with pseudopods, negative for alpha-NAE expression and positive for Px. TPA effect on U-937 cells was similar to that observed with GM-CSF. No proliferative response was detected with any of the factors assayed. These results suggest that GM-CSF and IL-4 can promote distinct changes in the differentiative pathway of U-937 cells, as evidenced by the marked morphological, immunological and cytochemical changes observed in the cell cultures.
Koss
A
A
Unidad de Investigaciones Oncohematológicas. Oncolab. Buenos Aires, Argentina.
Lucero
G
G
Koziner
B
B
D015415:Biomarkers; D002277:Carcinoma / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D007948:Leukemia, Monocytic, Acute / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009283:Naphthol AS D Esterase / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
D015415:Biomarkers; D017077:Culture Media, Conditioned; D016207:Cytokines; D016167:Integrin alphaXbeta2; D018950:Lipopolysaccharide Receptors; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase; D009283:Naphthol AS D Esterase; D013755:Tetradecanoylphorbol Acetate