Involvement of the urokinase-type plasminogen activator receptor in hematopoietic stem cell mobilization (Articolo in rivista)

Type
Label
  • Involvement of the urokinase-type plasminogen activator receptor in hematopoietic stem cell mobilization (Articolo in rivista) (literal)
Anno
  • 2005-01-01T00:00:00+01:00 (literal)
Alternative label
  • Selleri C, Montuori N, Ricci P, Visconte V, Carriero MV, Sidenius N, Serio B, Blasi F, Rotoli B, Rossi G, Ragno P. (2005)
    Involvement of the urokinase-type plasminogen activator receptor in hematopoietic stem cell mobilization
    in Blood
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Selleri C, Montuori N, Ricci P, Visconte V, Carriero MV, Sidenius N, Serio B, Blasi F, Rotoli B, Rossi G, Ragno P. (literal)
Pagina inizio
  • 2198 (literal)
Pagina fine
  • 2205 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • Involvement of the urokinase-type plasminogen activator receptor in hematopoietic stem cell mobilization (literal)
Abstract
  • We investigated the involvement of the urokinase-type plasminogen-activator receptor (uPAR) in granulocyte-colony-stimulating factor (G-CSF)-induced mobilization of CD34+ hematopoietic stem cells (HSCs) from 16 healthy donors. Analysis of peripheral blood mononuclear cells (PBMNCs) showed an increased uPAR expression after G-CSF treatment in CD33+ myeloid and CD14+ monocytic cells, whereas mobilized CD34+ HSCs remained uPAR negative. G-CSF treatment also induced an increase in serum levels of soluble uPAR (suPAR). Cleaved forms of suPAR (c-suPAR) were released in vitro by PBMNCs and were also detected in the serum of G-CSF-treated donors. c-suPAR was able to chemoattract CD34+ KG1 leukemia cells and CD34+ HSCs, as documented by their in vitro migratory response to a chemotactic suPAR-derived peptide (uPAR84-95). uPAR84-95 induced CD34+ KG1 and CD34+ HSC migration by activating the high-affinity fMet-Leu-Phe (fMLP) receptor (FPR). In addition, uPAR84-95 inhibited CD34+ KG1 and CD34+ HSC in vitro migration toward the stromal-derived factor 1 (SDF1), thus suggesting the heterologous desensitization of its receptor, CXCR4. Finally, uPAR84-95 treatment significantly increased the output of clonogenic progenitors from long-term cultures of CD34+ HSCs. Our findings demonstrate that G-CSF-induced upregulation of uPAR on circulating CD33+ and CD14+ cells is associated with increased uPAR shedding, which leads to the appearance of serum c-suPAR. c-suPAR could contribute to the mobilization of HSCs by promoting their FPR-mediated migration and by inducing CXCR4 desensitization. (literal)
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