Mobilization of hematopoietic stem cells as a result of innate immunity-mediated sterile inflammation in the bone marrow microenvironment - The involvement of extracellular nucleotides and purinergic signaling

Mariusz Z. Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations

Abstract

Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes. All these factors together trigger activation of the complement and coagulation cascades, both of which orchestrate egress of HSPCs into BM sinusoids and lymphatics. Recent evidence also indicates that, in addition to attenuation of the SDF-1-CXCR4 and VLA-4-VCAM-1 retention axes in the BM microenvironment and the presence of a mobilization-directing phosphosphingolipid gradient in PB, an important role in the mobilization process is played by extracellular nucleotides and purinergic signaling. In particular, a new finding by our laboratory is that, while extracellular ATP promotes mobilization of HSPCs, its derivative, adenosine, has the opposite (inhibitory) effect.

Original languageEnglish
Pages (from-to)1116-1123
Number of pages8
JournalLeukemia
Volume32
Issue number5
DOIs
StatePublished - May 1 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Mobilization of hematopoietic stem cells as a result of innate immunity-mediated sterile inflammation in the bone marrow microenvironment - The involvement of extracellular nucleotides and purinergic signaling'. Together they form a unique fingerprint.

Cite this