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The pharmacological activation of adenosine A1 and A3 receptors does not modulate the long- or short-term repopulating ability of hematopoietic stem and multipotent progenitor cells in mice

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Abstract

This study continues our earlier findings on the hematopoiesis-modulating effects of adenosine A1 and A3 receptor agonists that were performed on committed hematopoietic progenitor and precursor cell populations. In the earlier experiments, N 6-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, was found to inhibit proliferation in the above-mentioned hematopoietic cell systems, whereas N 6-(3-iodobenzyl)adenosine-5′-N-methyluronamide (IB-MECA), an adenosine A3 receptor agonist, was found to stimulate it. The topic of this study was to evaluate the possibility that the above-mentioned adenosine receptor agonists modulate the behavior of early hematopoietic progenitor cells and hematopoietic stem cells. Flow cytometric analysis of hematopoietic stem cells in mice was employed, as well as a functional test of hematopoietic stem and progenitor cells (HSPCs). These techniques enabled us to study the effect of the agonists on both short-term repopulating ability and long-term repopulating ability, representing multipotent progenitors and hematopoietic stem cells, respectively. In a series of studies, we did not find any significant effect of adenosine agonists on HSPCs in terms of their numbers, proliferation, or functional activity. Thus, it can be concluded that CPA and IB-MECA do not significantly influence the primitive hematopoietic stem and progenitor cell pool and that the hematopoiesis-modulating action of these adenosine receptor agonists is restricted to more mature compartments of hematopoietic progenitor and precursor cells.

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Acknowledgments

This work was supported by the Grant Agency of the Czech Republic (grants nos. 305/08/0158 and P303/11/0128), by the Ministry of Defense of the Czech Republic (project no. 1001 8 5090), by the Ministry of Education, Youth and Sports of the Czech Republic (projects MSM 0021620806, LC06044, and PRVOUK-P24/LF1/3), and by Charles University in Prague (grant SVV-2012-264507).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i, Academy of Sciences of the Czech Republic, Královopolská 135, 61265, Brno, Czech Republic

    Michal Hofer, Milan Pospíšil, Zuzana Hoferová & Denisa Komůrková

  2. Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Praha 2, Czech Republic

    Petr Páral, Filipp Savvulidi & Luděk Šefc

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  1. Michal Hofer
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  2. Milan Pospíšil
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  3. Zuzana Hoferová
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  4. Denisa Komůrková
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  5. Petr Páral
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  6. Filipp Savvulidi
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  7. Luděk Šefc
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Correspondence to Luděk Šefc.

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Hofer, M., Pospíšil, M., Hoferová, Z. et al. The pharmacological activation of adenosine A1 and A3 receptors does not modulate the long- or short-term repopulating ability of hematopoietic stem and multipotent progenitor cells in mice. Purinergic Signalling 9, 207–214 (2013). https://doi.org/10.1007/s11302-012-9340-5

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  • DOI: https://doi.org/10.1007/s11302-012-9340-5

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