Cargando…

Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Thapa, Arjun, Abdelbaset-Ismail, Ahmed, Chumak, Vira, Adamiak, Mateusz, Brzezniakiewicz-Janus, Katarzyna, Ratajczak, Janina, Kucia, Magdalena, Ratajczak, Mariusz Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622533/
https://www.ncbi.nlm.nih.gov/pubmed/35870082
http://dx.doi.org/10.1007/s12015-022-10417-w
_version_ 1784821791698452480
author Thapa, Arjun
Abdelbaset-Ismail, Ahmed
Chumak, Vira
Adamiak, Mateusz
Brzezniakiewicz-Janus, Katarzyna
Ratajczak, Janina
Kucia, Magdalena
Ratajczak, Mariusz Z.
author_facet Thapa, Arjun
Abdelbaset-Ismail, Ahmed
Chumak, Vira
Adamiak, Mateusz
Brzezniakiewicz-Janus, Katarzyna
Ratajczak, Janina
Kucia, Magdalena
Ratajczak, Mariusz Z.
author_sort Thapa, Arjun
collection PubMed
description 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 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-022-10417-w.
format Online
Article
Text
id pubmed-9622533
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-96225332022-11-02 Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells Thapa, Arjun Abdelbaset-Ismail, Ahmed Chumak, Vira Adamiak, Mateusz Brzezniakiewicz-Janus, Katarzyna Ratajczak, Janina Kucia, Magdalena Ratajczak, Mariusz Z. Stem Cell Rev Rep Article 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 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-022-10417-w. Springer US 2022-07-23 2022 /pmc/articles/PMC9622533/ /pubmed/35870082 http://dx.doi.org/10.1007/s12015-022-10417-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Thapa, Arjun
Abdelbaset-Ismail, Ahmed
Chumak, Vira
Adamiak, Mateusz
Brzezniakiewicz-Janus, Katarzyna
Ratajczak, Janina
Kucia, Magdalena
Ratajczak, Mariusz Z.
Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells
title Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells
title_full Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells
title_fullStr Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells
title_full_unstemmed Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells
title_short Extracellular Adenosine (eAdo) - A(2B) Receptor Axis Inhibits in Nlrp3 Inflammasome-dependent Manner Trafficking of Hematopoietic Stem/progenitor Cells
title_sort extracellular adenosine (eado) - a(2b) receptor axis inhibits in nlrp3 inflammasome-dependent manner trafficking of hematopoietic stem/progenitor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622533/
https://www.ncbi.nlm.nih.gov/pubmed/35870082
http://dx.doi.org/10.1007/s12015-022-10417-w
work_keys_str_mv AT thapaarjun extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells
AT abdelbasetismailahmed extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells
AT chumakvira extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells
AT adamiakmateusz extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells
AT brzezniakiewiczjanuskatarzyna extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells
AT ratajczakjanina extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells
AT kuciamagdalena extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells
AT ratajczakmariuszz extracellularadenosineeadoa2breceptoraxisinhibitsinnlrp3inflammasomedependentmannertraffickingofhematopoieticstemprogenitorcells