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Chronic Lymphocytic Leukemia

Cleavage fragments of the third complement component (C3) enhance stromal derived factor-1 (SDF-1)-mediated platelet production during reactive postbleeding thrombocytosis

Leukemia volume 21, pages 973–982 (2007)Cite this article

Abstract

We hypothesized that the third complement component (C3) cleavage fragments (C3a and des-ArgC3a) are involved in stress/inflammation-related thrombocytosis, and investigated their potential role in reactive thrombocytosis induced by bleeding. We found that platelet counts are lower in C3-deficient mice in response to excessive bleeding as compared to normal littermates and that C3a and des-ArgC3a enhance stromal-derived factor-1 (SDF-1)-dependent megakaryocyte (Megs) migration, adhesion and platelet shedding. At the molecular level, C3a stimulates in Megs MAPKp42/44 phosphorylation, and enhances incorporation of CXCR4 into membrane lipid rafts increasing the responsiveness of Megs to SDF-1. We found that perturbation of lipid raft formation by statins decreases SDF-1/C3a-dependent platelet production in vitro and in an in vivo model statins ameliorated post-bleeding thrombocytosis. Thus, inhibition of lipid raft formation could find potential clinical application as a means of ameliorating some forms of thrombocytosis.

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Acknowledgements

This work was supported by an NIH Grant R01 DK074720-01 to MZR.

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Authors and Affiliations

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

    M Wysoczynski, M Kucia, J Ratajczak & M Z Ratajczak

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

    M Z Ratajczak

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  1. M Wysoczynski
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  2. M Kucia
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Correspondence to M Z Ratajczak.

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Wysoczynski, M., Kucia, M., Ratajczak, J. et al. Cleavage fragments of the third complement component (C3) enhance stromal derived factor-1 (SDF-1)-mediated platelet production during reactive postbleeding thrombocytosis. Leukemia 21, 973–982 (2007). https://doi.org/10.1038/sj.leu.2404629

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