Increased soluble urokinase plasminogen activator receptor (suPAR) serum levels after granulocyte colony-stimulating factor treatment do not predict successful …

T Fietz, K Hattori, E Thiel, B Heissig - Blood, 2006 - ashpublications.org
T Fietz, K Hattori, E Thiel, B Heissig
Blood, 2006ashpublications.org
Hematopoietic stem cell (HSC) mobilization is still not well understood. Accumulating
evidence suggests that protease activation is an important step: proteases release cytokines
or chemokines from the extracellular matrix, thereby modulating biological responses. 1, 2
The urokinase-type plasminogen activator receptor (uPAR) is the receptor for urokinasetype
plasminogen activator (uPA). The ligand uPA cleaves uPAR between domains I and II,
liberating domain I—uPAR (I)—while uPAR (II-III) remains on the cell surface. 3 Proteases …
Hematopoietic stem cell (HSC) mobilization is still not well understood. Accumulating evidence suggests that protease activation is an important step: proteases release cytokines or chemokines from the extracellular matrix, thereby modulating biological responses. 1, 2 The urokinase-type plasminogen activator receptor (uPAR) is the receptor for urokinasetype plasminogen activator (uPA). The ligand uPA cleaves uPAR between domains I and II, liberating domain I—uPAR (I)—while uPAR (II-III) remains on the cell surface. 3 Proteases cleave uPAR (I-III) and soluble urokinase plasminogen activator receptor (suPAR)(I-III) in vitro, 3-5 unmasking a region with chemotactic properties. 6 Recently, a role of suPAR for granulocyte colony-stimulating factor (G-CSF)–mediated HSC mobilization in allogeneic donors has been proposed in this journal. 7 Results we obtained in autologous patients receiving chemotherapy prior to G-CSF, however, challenge the proposed role for suPAR in certain settings of G-CSF–mediated HSC mobilization. Serum samples were collected at our center before G-CSF and/or prior to leukapheresis from healthy allogeneic donors and autologous patients, most of whom were suffering from lymphoid malignancies in remission of the disease. The G-CSF dose for donors was 2 5 or 2 8 g/kg body weight per day (BW/d) subcutaneously. Leukapheresis was performed on day 5 of G-CSF. Autologous patients were mobilized with chemotherapy chosen for optimal stem cell mobilization and disease control. G-CSF (5 or 10 g/kg BW/d subcutaneously) was started 6 days before scheduled leukapheresis. Blinded serum samples were analyzed with time-resolved fluoroimmunoassays by measuring uPAR variants concentrations before and after uPAR depletion. 8 Accuracy was determined by measuring recoveries of spiked standards in 20%(vol/vol) serum pool in buffer.
Progenitor cell mobilization was similar in autologous patients (mean CD34 cell count on the day of leukapheresis, 84 128 15893/mL [SEM] blood; n 66) and allogeneic donors (79 470 10 710/mL; n 21). However, leukocyte counts on the day of leukapheresis were inferior for autologous pts (20.89 1.46/nL, n 66, compared with 49.6 2.5/nL in allogeneic donors; n 28, P. 001, unpaired t test).
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