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.

Document Type

Review

Publication Date

3-5-2018

Notes/Citation Information

Published in Leukemia, v. 32, issue 5, p. 1116-1123.

© The Author(s) 2018.

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41375-018-0087-z

Funding Information

This work was supported by NIH grants 2R01 DK074720 and R01HL112788, the Stella and Henry Endowment, and the OPUS grant DEC-2016/23/B/NZ3/03157 to MZR. MP was supported by NIH T32 HL134644 to MZR.

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