Enhanced ability of daniplestim and myelopoietin-1 to suppress apoptosis in human hematopoietic cells
| Autor: | PD Doshi, S M Oberhaus, M. Pearce, Linda S. Steelman, J A McCubrey, Oussama A. Saleh, JP McKearn, Richard A. Franklin, William L. Blalock, P W Moye, John T. Lee, C. Burrows |
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| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
medicine.medical_treatment Recombinant Fusion Proteins Apoptosis Biology Hematopoietic Cell Growth Factors Precursor cell Granulocyte Colony-Stimulating Factor medicine Humans Cell Lineage Interleukin 3 Hematopoietic Stem Cell Transplantation Cell Differentiation Hematology Hematopoietic Stem Cells Hematopoietic Stem Cell Mobilization Peptide Fragments Recombinant Proteins Cell biology Granulocyte colony-stimulating factor Hematopoiesis Haematopoiesis Cytokine Oncology Immunology Interleukin-3 Stem cell Signal transduction Peptides |
| Zdroj: | Leukemia. 15(8) |
| ISSN: | 0887-6924 |
| Popis: | Modified and chimeric cytokines have been developed to aid in the recovery of hematopoietic precursor cells after myeloablative chemotherapy. The interleukin-3 (IL-3) receptor agonist, daniplestim, binds to the IL-3 receptor-alpha subunit with 60-fold greater affinity and induces cell proliferation and colony-forming unit formation 10- to 22-fold better than native IL-3. A chimeric cytokine, myelopoietin-1, composed of daniplestim and a G-CSF receptor agonist binds both the IL-3 and G-CSF receptors. While the in vivo effects of daniplestim and myelopoietin-1 are well described, the mechanisms by which they stimulate growth are not well understood. We have investigated the effects of daniplestim and myelopoietin-1 on the prevention of apoptosis in two human hematopoietic cell lines, OCI-AML.5 and AML 193. Daniplestim and myelopoietin-1 prevented apoptosis to a greater degree than native recombinant IL-3 or G-CSF as determined by annexin V/propidium iodide binding and TUNEL assays. Daniplestim and myelopoietin-1 promoted the maintenance of the mitochondrial membrane potential better than native IL-3 or G-CSF. These cytokines promoted a lower redox potential as higher levels of free radicals were detected after cytokine treatment than in cytokine-deprived cells implying increased respiration. These results indicate that daniplestim and myelopoietin-1 are able to prevent apoptosis in hematopoietic cells more effectively than native IL-3 and G-CSF. These effects of daniplestim and myelopoietin-1 may contribute to their effective ability to repopulate hematopoietic precursor cells after chemotherapy. |
| Databáze: | OpenAIRE |
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