| Full text | |
| Author(s): |
Adamiak, Mateusz
[1, 2]
;
Bujko, Kamila
[1, 2]
;
Thapa, Arjun
[2]
;
Pensato, Valentina
[2]
;
Brzezniakiewicz-Janus, Katarzyna
[3]
;
Ratajczak, Janina
[2]
;
Davies, Daryl L.
[4]
;
Ulrich, Henning
[5]
;
Kucia, Magda
[1, 2]
;
Ratajczak, Mariusz Z.
[1, 2, 3]
Total Authors: 10
|
| Affiliation: | [1] Med Univ Warsaw, Dept Regenerat Med, Warsaw - Poland
[2] Univ Louisville, James Graham Brown Canc Ctr, Stem Cell Inst, Louisville, KY 40292 - USA
[3] Univ Zielona Gora, Hosp Gorzow Wlkp, Dept Hematol, Zielona Gora - Poland
[4] Univ Southern Calif, Titus Family Dept Clin Pharm, Sch Pharm, Los Angeles, CA 90007 - USA
[5] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | LEUKEMIA; v. 36, n. 1 JUL 2021. |
| Web of Science Citations: | 1 |
| Abstract | |
Recent evidence indicates that extracellular adenosine triphosphate (eATP), as a major mediator of purinergic signaling, plays an important role in regulating the mobilization and homing of hematopoietic stem progenitor cells (HSPCs). In our previous work we demonstrated that eATP activates the P2X7 ion channel receptor in HSPCs and that its deficiency impairs stem cell trafficking. To learn more about the role of the P2X purinergic receptor family in hematopoiesis, we phenotyped murine and human HSPCs with respect to the seven P2X receptors and observed that, these cells also highly express P2X4 receptors, which shows similar to 50% sequence similarity to P2X7 subtypes, but that P2X4 cells are more sensitive to eATP and signal much more rapidly. Using the selective P2X4 receptor antagonist PSB12054 as well as P2X4-KO mice, we found that the P2X4 receptor, similar to P2X7 receptor, promotes trafficking of HSPCs in that its deficiency leads to impaired chemotaxis of HSPCs in response to a stromal-derived factor 1 (SDF-1) gradient, less effective pharmacological mobilization, and defective homing and engraftment of HSPCs after transplantation into myeloablated hosts. This correlated with a decrease in SDF-1 expression in the BM microenvironment. Overall, our results confirm the proposed cooperative dependence of both receptors in response to eATP signaling. In G-CSF-induced mobilization, a lack of one receptor is not compensated by the presence of the other one, which supports their mutual dependence in regulating HSPC trafficking. (AU) | |
| FAPESP's process: | 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases |
| Grantee: | Alexander Henning Ulrich |
| Support Opportunities: | Research Projects - Thematic Grants |