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

  • Mariusz Z. RatajczakEmail author
  • ChiHwa Kim
  • Janina Ratajczak
  • Anna Janowska-Wieczorek
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 735)


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.


Lipid Raft Bone Marrow Stromal Cell Membrane Attack Complex Complement Cascade Bone Marrow Microenvironment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Mariusz Z. Ratajczak
    • 1
    Email author
  • ChiHwa Kim
    • 1
  • Janina Ratajczak
    • 1
  • Anna Janowska-Wieczorek
    • 2
  1. 1.Stem Cell Biology Program at the James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of MedicineUniversity of AlbertaEdmontonCanada

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