Novel evidence that extracellular nucleotides and purinergic signaling induce innate immunity-mediated mobilization of hematopoietic stem/progenitor cells.

ABSTRACT: Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced "sterile inflammation" in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers. Furthermore, after its release into the extracellular space, ATP is processed by ectonucleotidases: CD39 converts ATP to AMP, and CD73 converts AMP to adenosine. We observed that CD73-deficient mice mobilize more HSPCs than do wild-type mice du

SUBMITTER: Adamiak M 

PROVIDER: S-EPMC6127086 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature