Erythropoietin-independent erythroid colony formation by bone marrow progenitors exposed to interleukin-11 and interleukin-8
| Autor: | Isabelle Corre-Buscail, Marjorie Boissinot, Danielle Pineau, Sylvie Hermouet |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Stromal cell Cell Culture Techniques Stem cell factor Bone Marrow Cells Biology hemic and lymphatic diseases Genetics medicine Humans Interleukin 8 Progenitor cell Molecular Biology Erythropoietin Polycythemia Vera Erythroid Precursor Cells Interleukin-8 Interleukin Cell Biology Hematology Hematopoietic Stem Cells Interleukin-11 Molecular biology Coculture Techniques medicine.anatomical_structure Immunology Cytokines Bone marrow medicine.drug Signal Transduction |
| Zdroj: | Experimental hematology. 33(11) |
| ISSN: | 0301-472X |
| Popis: | Objective Endogenous erythroid colonies (EECs), formed in vitro without erythropoietin (EPo) or other exogenous cytokines, are characteristic of Polycythemia vera (PV). Our aim was to identify specific conditions of culture of bone marrow (BM) progenitors allowing formation of erythroid colonies without EPo. Methods BM mononuclear cells (BMMCs), purified CD34+ cells, and purified CD36+ erythroid progenitors were cultured in serum-free media without and with cytokines: EPo, stem cell factor (SCF), and interleukin (IL)-11 and IL-8, produced by BM stromal cells and found elevated in PV. Results EECs were formed in PV cultures of either BMMCs or CD34+ cells, which include cytokine-secreting cells, but not in cultures of purified CD36+ erythroid progenitors (EP). Despite expression of V617F JAK-2, no constitutive activation of JAK-2, Stat-5, or Erk-1/2 was detected in erythroblasts issued from PV CD36+ progenitors. However, when SCF was provided, PV CD36+ progenitors formed erythroid colonies without EPo. The ability to form erythroid colonies with SCF alone was conferred to BM progenitors of healthy donors and secondary erythrocytosis by exposure to IL-11 and IL-8. Both IL-11 and IL-8 enhanced formation of erythroid colonies in response to EPo and interfered with the activation of Erk-1/2 and Stat-5 induced, respectively, by SCF and EPo in erythroblasts. Anti-IL-11 antibody inhibited formation of erythroid colonies by PV BMMCs and CD34+ cells. Conclusion The data indicate that PV erythroid progenitors remain cytokine-dependent and that normal BM progenitors exposed to IL-11 and IL-8 can acquire the ability to form erythroid colonies without EPo. |
| Databáze: | OpenAIRE |
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