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Innate Immunity as Orchestrator of Bone Marrow Homing for Hematopoietic Stem/Progenitor Cells

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Complement Therapeutics

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 735))

Abstract

The first step that precedes hematopoietic transplantation is elimination of pathological hematopoiesis by administration of myeloablative doses of radiochemotherapy. This eliminates hematolymphopoietic cells and at the same time damages hematopoietic microenvironment in bone marrow (BM). The damage of BM tissue leads to activation of complement cascade (CC), and bioactive CC cleavage fragments modulate several steps of BM recovery after transplantation of hematopoietic stem progenitor cells (HSPCs). Accordingly, C3 cleavage fragments (soluble C3a/desArgC3a and solid phase iC3b) and generation of soluble form of C5b-C9 also known as membrane attack complex (MAC) as well as release of antimicrobial cationic peptides from stromal cells (cathelicidin or LL-37 and β-2 defensin) promote homing of HSPCs. To support this, C3 cleavage fragments and antimicrobial cationic peptides increase homing responsiveness of transplanted HSPCs to stroma-derived factor-1 (SDF-1) gradient. Furthermore, damaged BM cells release several other chemoattractants for HSPCs such as bioactive lipids sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) and chemotactic purines (ATP and UTP). In this chapter, we will discuss the current view on homing of transplanted HSPCs into BM that in addition to SDF-1 is orchestrated by CC, antimicrobial cationic peptides, and several other prohoming factors. We also propose modulation of CC as a novel strategy to optimize/accelerate homing of HSPCs.

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Acknowledgments

This work was supported by NIH R01 DK074720 and Stella and Henry Hoenig Endowment to MZR.

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Authors and Affiliations

  1. Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA

    Mariusz Z. Ratajczak M.D., Ph.D., ChiHwa Kim & Janina Ratajczak

  2. Department of Medicine, University of Alberta, Edmonton, Canada

    Anna Janowska-Wieczorek

Authors
  1. Mariusz Z. Ratajczak M.D., Ph.D.
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  2. ChiHwa Kim
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  3. Janina Ratajczak
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  4. Anna Janowska-Wieczorek
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Correspondence to Mariusz Z. Ratajczak M.D., Ph.D. .

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Editors and Affiliations

  1. Medicine, University Of Pennsylvania Department Of Pathology Laboratory Of, Philadelphia, Pennsylvania, USA

    John D. Lambris

  2. University of Colorado School of Medicin, Aurora, Colorado, USA

    V. Michael Holers

  3. Department of Pathology & Laboratory Med, University of Pennsylvania School of Med, Philadelphia, Pennsylvania, USA

    Daniel Ricklin

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Ratajczak, M.Z., Kim, C., Ratajczak, J., Janowska-Wieczorek, A. (2013). Innate Immunity as Orchestrator of Bone Marrow Homing for Hematopoietic Stem/Progenitor Cells. In: Lambris, J., Holers, V., Ricklin, D. (eds) Complement Therapeutics. Advances in Experimental Medicine and Biology, vol 735. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4118-2_15

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