Innate immunity as orchestrator of bone marrow homing for hematopoietic stem/progenitor cells

Ratajczak, MZ; Kim, C; Ratajczak, J; Janowska-Wieczorek, A

HERO ID

2901859

Reference Type

Journal Article

Subtype

Review

Year

2013

Language

English

PMID

23402030

HERO ID 2901859
Material Type Review
In Press No
Year 2013
Title Innate immunity as orchestrator of bone marrow homing for hematopoietic stem/progenitor cells
Authors Ratajczak, MZ; Kim, C; Ratajczak, J; Janowska-Wieczorek, A
Journal Advances in Experimental Medicine and Biology
Volume 735
Page Numbers 219-232
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.
Pmid 23402030
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English