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Stem Cells

Novel insight into stem cell mobilization-Plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex

Leukemia volume 24, pages 976–985 (2010)Cite this article

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Abstract

The complement cascade (CC) becomes activated and its cleavage fragments play a crucial role in the mobilization of hematopoietic stem/progenitor cells (HSPCs). Here, we sought to determine which major chemoattractant present in peripheral blood (PB) is responsible for the egress of HSPCs from the bone marrow (BM). We noticed that normal and mobilized plasma strongly chemoattracts HSPCs in a stromal-derived factor-1 (SDF-1)-independent manner because (i) plasma SDF-1 level does not correlate with mobilization efficiency; (ii) the chemotactic plasma gradient is not affected in the presence of AMD3100 and (iii) it is resistant to denaturation by heat. Surprisingly, the observed loss of plasma chemotactic activity after charcoal stripping suggested the involvement of bioactive lipids and we focused on sphingosine-1-phosphate (S1P), a known chemoattracant of HSPCs. We found that S1P (i) creates in plasma a continuously present gradient for BM-residing HSPCs; (ii) is at physiologically relevant concentrations a chemoattractant several magnitudes stronger than SDF-1 and (iii) its plasma level increases during mobilization due to CC activation and interaction of the membrane attack complex (MAC) with erythrocytes that are a major reservoir of S1P. We conclude and propose a new paradigm that S1P is a crucial chemoattractant for BM-residing HSPCs and that CC through MAC induces the release of S1P from erythrocytes for optimal egress/mobilization of HSPCs.

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Acknowledgements

This work was supported by NIH Grants R01 CA106281 and R01 DK074720, and Stella and Henry Endowment and European Union structural funds, Innovative Economy Operational Program POIG.01.01.02-00-109/09-00 to MZR and NIH 1RC1 HL099447 to MJL and CBS/CIHR XE00025 grant to A.J.-W.

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Authors and Affiliations

  1. Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    M Z Ratajczak, H Lee, M Wysoczynski, W Wan, M Kucia & J Ratajczak

  2. Department of Physiology Pomeranian Medical University, Szczecin, Poland

    W Marlicz

  3. Cleveland Cord Blood Center, Case Western University, Cleveland, OH, USA

    M J Laughlin

  4. Department of Medicine, University of Alberta, Edmonton, AB, Canada

    A Janowska-Wieczorek

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  1. M Z Ratajczak
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Ratajczak, M., Lee, H., Wysoczynski, M. et al. Novel insight into stem cell mobilization-Plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex. Leukemia 24, 976–985 (2010). https://doi.org/10.1038/leu.2010.53

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