Activation of adenosine A₃ receptors supports hematopoiesis-stimulating effects of granulocyte colony-stimulating factor in sublethally irradiated mice

Abstract

Purpose: Research areas of ‘post-exposure treatment’ and ‘cytokines and growth factors’ have top priority among studies aimed at radiological nuclear threat countermeasures. The experiments were aimed at testing the ability of N⁶-(3-iodobenzyl)adenosine-5′-N-methyluronamide (IB-MECA), an adenosine A₃ receptor agonist, to modulate hematopoiesis in sublethally irradiated mice, when administered alone or in a combination with granulocyte colony-stimulating factor (G-CSF) in a two-day post-irradiation treatment regimen.

Materials and methods: A complete analysis of hematopoiesis including determination of numbers of bone marrow hematopoietic progenitor and precursor cells, as well as of numbers of peripheral blood cells, was performed. The outcomes of the treatment were assessed at days 3 to 22 after irradiation.

Results: IB-MECA alone has been found to induce a significant elevation of numbers of bone marrow granulocyte-macrophage progenitor cells (GM-CFC) and peripheral blood neutrophils. IB-MECA given concomitantly with G-CSF increased significantly bone marrow GM-CFC and erythroid progenitor cells (BFU-E) in comparison with the controls and with animals administered each of the drugs alone.

Conclusions: The findings suggest the ability of IB-MECA to stimulate hematopoiesis and to support the hematopoiesis-stimulating effects of G-CSF in sublethally irradiated mice.

Keywords:

• ionising radiation
• hematopoiesis
• adenosine A₃ receptors
• IB-MECA

Acknowledgements

The work was supported by the Grant Agency of the Czech Republic (grant no. 305/08/0158) and by the Academy of Sciences of the Czech Republic (grants nos. AV0Z50050507 and AV0Z50040702).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.