Academic Journal
Extracellular Adenosine (eAdo) - A2B Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells
| العنوان: | Extracellular Adenosine (eAdo) - A2B Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells |
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| المؤلفون: | Thapa, Arjun, Abdelbaset-Ismail, Ahmed, Chumak, Vira, Adamiak, Mateusz, Brzezniakiewicz-Janus, Katarzyna, Ratajczak, Janina, Kucia, Magdalena, Ratajczak, Mariusz Z. |
| المساهمون: | Narodowym Centrum Nauki |
| المصدر: | Stem Cell Reviews and Reports ; volume 18, issue 8, page 2893-2911 ; ISSN 2629-3269 2629-3277 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | 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 A 2B receptor and a specific inhibitor of this receptor improves eAdo-aggravated trafficking of HSPCs. To explain this at the molecular level eAdo-A 2B 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 A 2B inhibition promotes cell migration and proliferation. Based on this we postulate that blockage of A 2B receptor may accelerate the mobilization of ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1007/s12015-022-10417-w |
| DOI: | 10.1007/s12015-022-10417-w.pdf |
| DOI: | 10.1007/s12015-022-10417-w/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1007/s12015-022-10417-w https://link.springer.com/content/pdf/10.1007/s12015-022-10417-w.pdf https://link.springer.com/article/10.1007/s12015-022-10417-w/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.CA41AE61 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s12015-022-10417-w |
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