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

Höfer, Milan; Pospı́šil, M.; Hoferová, Zuzana; Komůrková, Denisa; Páral, Petr; Savvulidi, Filipp; Šefc, Luděk

doi:10.1007/s11302-012-9340-5

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…In the latter studies, stimulation by IB-MECA was observed in various parameters of the bone marrow progenitor and precursor cells and of the peripheral blood. The compartment of hematopoietic stem cells in mice was not found to be influenced by the administration of IB-MECA [12].…”

Section: Introductionmentioning

confidence: 90%

Lack of adenosine A3 receptors causes defects in mouse peripheral blood parameters

Höfer

Pospı́šil

Dušek

et al. 2014

Purinergic Signalling

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The role of the adenosine A 3 receptor in hematopoiesis was studied using adenosine A 3 receptor knockout (A 3 AR KO) mice. Hematological parameters of peripheral blood and femoral bone marrow of irradiated and untreated A 3 AR KO mice and their wild-type (WT) counterparts were investigated. Irradiation of the mice served as a defined hematopoiesis-damaging means enabling us to evaluate contingent differences in the pattern of experimentally induced hematopoietic suppression between the A 3 AR KO mice and WT mice. Defects were observed in the counts and/or functional parameters of blood cells in the A 3 AR KO mice. These defects include statistically significantly lower values of blood neutrophil and monocyte counts, as well as those of mean erythrocyte volume, mean erythrocyte hemoglobin, blood platelet counts, mean platelet volume, and plateletcrit, and can be considered to bear evidence of the lack of a positive role played by the adenosine A 3 receptor in the hematopoietic system. Statistically significantly increased values of the bone marrow parameters studied in A 3 AR KO mice (femoral bone marrow cellularity, granulocyte/macrophage progenitor cells, and erythrocyte progenitor cells) can probably be explained by compensatory mechanisms attempting to offset the disorders in the function of blood elements in these mice. The pattern of the radiation-induced hematopoietic suppression was very similar in A 3 AR KO mice and their WT counterparts.

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Section: Introductionmentioning

confidence: 90%

Lack of adenosine A3 receptors causes defects in mouse peripheral blood parameters

Höfer

Pospı́šil

Dušek

et al. 2014

Purinergic Signalling

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“…Moreover, in adult mice, A 1 and A 3 receptors play a homeostatic opposite role in suppressing or stimulating hematopoiesis, respectively [ 2 , 16 , 17 ]. As reported selective activation of A 3 receptors promotes hematopoiesis by acting on differentiated hematopoietic progenitors [ 2 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Adenosine (eAdo) - A2B Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells

Thapa

Abdelbaset‐Ismail

Chumak

et al. 2022

Stem Cell Rev and Rep

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We postulated that mobilization, homing, and engraftment of hematopoietic stem/progenitor cells (HSCPs) is facilitated by a state of sterile inflammation induced in bone marrow (BM) after administration of pro-mobilizing drugs or in response to pre-transplant myeloablative conditioning. An important role in this phenomenon plays purinergic signaling that by the release of extracellular adenosine triphosphate (eATP) activates in HSPCs and in cells in the hematopoietic microenvironment an intracellular pattern recognition receptor (PPR) known as Nlrp3 inflammasome. We reported recently that its deficiency results in defective trafficking of HSPCs. Moreover, it is known that eATP after release into extracellular space is processed by cell surface expressed ectonucleotidases CD39 and CD73 to extracellular adenosine (eAdo) that in contrast to eATP shows an anti-inflammatory effect. Based on data that the state of sterile inflammation promotes trafficking of HSPCs, and since eAdo is endowed with anti-inflammatory properties we become interested in how eAdo will affect the mobilization, homing, and engraftment of HSPCs and which of eAdo receptors are involved in these processes. As expected, eAdo impaired HSPCs trafficking and this occurred in autocrine- and paracrine-dependent manner by direct stimulation of these cells or by affecting cells in the BM microenvironment. We report herein for the first time that this defect is mediated by activation of the A2B receptor and a specific inhibitor of this receptor improves eAdo-aggravated trafficking of HSPCs. To explain this at the molecular level eAdo-A2B receptor interaction upregulates in HSPCs in NF-kB-, NRF2- and cAMP-dependent manner heme oxygenase-1 (HO-1), that is Nlrp3 inflammasome inhibitor. This corroborated with our analysis of proteomics signature in murine HSPCs exposed to eAdo that revealed that A2B inhibition promotes cell migration and proliferation. Based on this we postulate that blockage of A2B receptor may accelerate the mobilization of HSPCs as well as their hematopoietic reconstitution and this approach could be potentially considered in the future to be tested in the clinic. Graphical Abstract

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“…The studies performed on the hematopoiesis of the A 3 AR KO mice so far have not comprised the parameter of the hematopoietic stem cells. However, recent investigations in normal mice have not demonstrated any efficacy of the administration of IB-MECA, an adenosine A 3 receptor agonist on the hematopoietic stem cell compartment (Hofer et al 2013b).…”

Section: Discussionmentioning

confidence: 98%

Hematopoiesis in 5-Fluorouracil-Treated Adenosine A3 Receptor Knock-Out Mice

Höfer

Pospı́šil²,

Dušek³

et al. 2015

Physiol Res

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The purpose of the study was to describe and compare normal and 5-fluorouracil (5-FU)-suppressed hematopoiesis in adenosine A3 receptor knock-out (A3AR KO) mice and their wild-type (WT) counterparts. To meet the purpose, a complex hematological analysis comprising nineteen peripheral blood and bone marrow parameters was performed in the mice. Defects previously observed in the peripheral blood erythrocyte and thrombocyte parameters of the A3AR KO mice were confirmed. Compartments of the bone marrow progenitor cells for granulocytes/macrophages and erythrocytes were enhanced in the control, as well as in the 5-FU-administered A3AR KO mice. 5-FU-induced hematopoietic suppression, evaluated on day 2 after the administration of the cytotoxic drug, was found to be significantly deeper in the A3AR KO mice compared with their WT counterparts, as measured at the level of the bone marrow progenitor cells. The rate of regeneration, as assessed between days 2 and 7 after 5-FU administration, was observed in the population of the granulocyte/macrophage progenitor cells to be higher in the A3AR KO mice in comparison with the WT ones. The increased depth of 5-FU-induced suppression in the compartments of the hematopoietic progenitor cells in the A3AR KO mice represents probably a hitherto undescribed further consequence of the lack of adenosine A3 receptors and indicates its synergism with the pharmacologically induced cytotoxic action of 5-FU.

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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

Abstract: This study continues our earlier findings on the hematopoiesis-modulating effects of adenosine A 1 and A 3 receptor agonists that were performed on committed hematopoietic progenitor and precursor cell populations. In the earlier experiments, N 6

Cited by 8 publications

References 26 publications

Lack of adenosine A3 receptors causes defects in mouse peripheral blood parameters

Lack of adenosine A3 receptors causes defects in mouse peripheral blood parameters

Extracellular Adenosine (eAdo) - A2B Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells

Hematopoiesis in 5-Fluorouracil-Treated Adenosine A3 Receptor Knock-Out Mice

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