title: Innate immunity as orchestrator of bone marrow homing for hematopoietic stem/progenitor cells.
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 beta-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.
authors: Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY 40202, USA. mzrata01@louisville.edu
authors: Mariusz Z
authors: MZ
authors: Ratajczak
authors: ChiHwa
authors: C
authors: Kim
authors: Janina
authors: J
authors: Ratajczak
authors: Anna
authors: A
authors: Janowska-Wieczorek
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000502:physiology; D001853:Bone Marrow / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D008055:Lipids / Q000502:physiology; D023083:beta-Defensins / Q000502:physiology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D054377:Chemokine CXCL12; C106641:DEFB4A protein, human; D008055:Lipids; D023083:beta-Defensins; D003165:Complement System Proteins; D054804:Cathelicidins
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