A novel role of purinergic signaling in mobilization, homing and engraftment of hematopoietic stem cells.

Bone marrow (BM) as an active hematopoietic organ is highly sensitive to changes in body microenvironments and responds to external physical stimuli from the surrounding environment. In particular, BM tissue responds to several cues related to infections, strenuous exercise, tissue/organ damage, circadian rhythms, and physical challenges such as irradiation. These multiple stimuli affect BM cells to a large degree through a coordinated response of the innate immunity network as an important guardian for maintaining homeostasis of the body. Innate immunity mediates these processes by engaging extracellular nucleotides, in addition to certain peptide-based factors, and bioactive phosphosphingolipids. Recent evidence demonstrates a significant role of extracellular ATP (eATP) secreted from cell in BM that is a major mediator of purinergic signaling being involved in the trafficking of hematopoietic stem/progenitor cells (HSPCs) during 1) pharmacological mobilization in their egress from the BM into peripheral blood (PB), and 2) in the reverse process of HSPCs homing and subsequent engraftment into BM after hematopoietic transplantation. While eATP stimulates positively these processes, its metabolite extracellular adenosine (eAdo) lays an opposite role. More importantly, the biological effects of eATP depend on activation in P2X7 and P2X4 receptor-dependent manner of intracellular pattern recognition receptor Nlrp3 inflammasome. Elucidation of these mechanisms will allow development of more efficient stem cell mobilization protocols to harvest the required number of HSPCs for transplantation and to accelerate hematopoietic reconstitution in patients undergoing hematopoietic transplantations. [ABSTRACT FROM AUTHOR]