期刊
LEUKEMIA
卷 32, 期 5, 页码 1116-1123出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41375-018-0087-z
关键词
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资金
- NIH [2R01 DK074720, R01HL112788, T32 HL134644]
- Stella and Henry Endowment
- OPUS grant [DEC-2016/23/B/NZ3/03157]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL112788, T32HL134644] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK074720] Funding Source: NIH RePORTER
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.
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