Adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5’-N-methyluronamide (IB-MECA) has been tested from the point of view of potentiating the effects of hematopoietic growth factors interleukin-3 (IL-3), stem cell factor (SCF), granulocyte- macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) on the growth of hematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) in suspension of normal mouse bone marrow cells in vitro. IB-MECA alone induced no GM-CFC growth. Significant elevation of numbers of GM-CFC evoked by the combinations of IB-MECA with IL-3, SCF, or GM-CSF as compared with these growth factors alone has been noted. Combinat ion of IB-MECA with G-CSF did not induce significantly higher numbers of GM-CFC in comparison with G-CSF alone. Joint action of three drugs, namely of IB-MECA + IL-3 + GM-CSF, produced significantly higher numbers of GM-CFC in comparison with the combinations of IB-MECA + IL-3, IB-MECA + GM-CSF, or IL-3 + GM-CSF. These results give evidence of a significant role of selective activation of adenosine A3 receptors in stimulation of the growth of granulocyte/macrophage hematopoietic progenitor cells., M. Hofer ... [et al.]., and Obsahuje seznam literatury
Our previous studies have shown that the combined administration of drugs elevating extracellular adenosine, i.e. dipyridamole (DP) and adenosine monophosphate (AMP), enhances murine hematopoiesis and potentiates the action of granulocyte colony-stimulating factor (G-CSF). In this study, colony-stimulating activity (CSA) of blood serum of mice treated with DP+AMP, G-CSF or all these drugs in combination, i.e. the ability of the sera to stimulate the growth of GM-CFC colonies, was assayed in vitro. Furthermore, the concentration of GM-CSF and IL-6 in the sera was determined. Administration of DP+AMP was found to enhance significantly serum CSA at all time intervals of serum sampling including 24 h after the last injection of the tested drugs. Additive effects of DP+AMP and G-CSF on serum CSA were noted at early intervals after administration of the drugs. Furthermore, IL-6 levels were significantly elevated in the sera of mice which were administered DP+AMP either alone or in combination with G-CSF. Our results show that the effects of DP+AMP are indirect, mediated through the induction of some cytokine(s) and/or growth factor(s) and that extracellular adenosine can act in cooperation with G-CSF. These findings contribute to the further elucidation of the role of adenosine in hematopoiesis., L. Weiterová, M. Hofer, M. Pospíšil, V. Znojil, D. Štreitová., and Obsahuje bibliografii a bibliografické odkazy