Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and nonpeptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation by migrating CD34+ cells, and increased cell adhesion to fibronectin. In vivo, preincubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (Galphai) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP- and CXCL12-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5'-triphosphatase (GTPase) Rac2 and downstream effectors Rho GTPase-activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the homing of HSCs to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving Galphai proteins and RhoGTPases

The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration / Rossi, L; Manfredini, Rossella; Bertolini, F; Ferrari, D; Fogli, M; Zini, Roberta; Salati, Simona; Salvestrini, V; Gulinelli, S; Adinolfi, E; Ferrari, Sergio; Di Virgilio, F; Baccarani, M; Lemoli, R. M.. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 109:(2007), pp. 533-542. [10.1182/blood-2006-01-035634]

The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration

MANFREDINI, Rossella;ZINI, Roberta;SALATI, Simona;FERRARI, Sergio;
2007

Abstract

Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and nonpeptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro, UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down-regulation by migrating CD34+ cells, and increased cell adhesion to fibronectin. In vivo, preincubation with UTP significantly enhanced the BM homing efficiency of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits (Galphai) may provide a converging signal for CXCR4- and P2Y-activated transduction pathways. In addition, gene expression profiling of UTP- and CXCL12-treated CD34+ cells and in vitro inhibition assays demonstrated that Rho guanosine 5'-triphosphatase (GTPase) Rac2 and downstream effectors Rho GTPase-activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent HSC migration. Our data suggest that UTP may physiologically modulate the homing of HSCs to the BM, in concert with CXCL12, via the activation of converging signaling pathways between CXCR4 and P2Y receptors, involving Galphai proteins and RhoGTPases
2007
109
533
542
The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration / Rossi, L; Manfredini, Rossella; Bertolini, F; Ferrari, D; Fogli, M; Zini, Roberta; Salati, Simona; Salvestrini, V; Gulinelli, S; Adinolfi, E; Ferrari, Sergio; Di Virgilio, F; Baccarani, M; Lemoli, R. M.. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 109:(2007), pp. 533-542. [10.1182/blood-2006-01-035634]
Rossi, L; Manfredini, Rossella; Bertolini, F; Ferrari, D; Fogli, M; Zini, Roberta; Salati, Simona; Salvestrini, V; Gulinelli, S; Adinolfi, E; Ferrari, Sergio; Di Virgilio, F; Baccarani, M; Lemoli, R. M.
File in questo prodotto:
File Dimensione Formato  
34. Blood_UTP_2007.pdf

Solo gestori archivio

Tipologia: Versione pubblicata dall'editore
Dimensione 368.02 kB
Formato Adobe PDF
368.02 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/718843
Citazioni
  • ???jsp.display-item.citation.pmc??? 49
  • Scopus 83
  • ???jsp.display-item.citation.isi??? 78
social impact