Nlrp3 Inflammasome Signaling Regulates the Homing and Engraftment of Hematopoietic Stem Cells (HSPCs) by Enhancing Incor
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Nlrp3 Inflammasome Signaling Regulates the Homing and Engraftment of Hematopoietic Stem Cells (HSPCs) by Enhancing Incorporation of CXCR4 Receptor into Membrane Lipid Rafts Mateusz Adamiak 1,2 & Ahmed Abdel-Latif 3 & Kamila Bujko 1 & Arjun Thapa 1 & Krzysztof Anusz 4 & Michał Tracz 4 & Katarzyna Brzezniakiewicz-Janus 5 & Janina Ratajczak 1 & Magda Kucia 1,2 & Mariusz Z. Ratajczak 1,2
# The Author(s) 2020
Abstract Fast and efficient homing and engraftment of hematopoietic stem progenitor cells (HSPCs) is crucial for positive clinical outcomes from transplantation. We found that this process depends on activation of the Nlrp3 inflammasome, both in the HSPCs to be transplanted and in the cells in the recipient bone marrow (BM) microenvironment. For the first time we provide evidence that functional deficiency in the Nlrp3 inflammasome in transplanted cells or in the host microenvironment leads to defective homing and engraftment. At the molecular level, functional deficiency of the Nlrp3 inflammasome in HSPCs leads to their defective migration in response to the major BM homing chemoattractant stromal-derived factor 1 (SDF-1) and to other supportive chemoattractants, including sphingosine-1-phosphate (S1P) and extracellular adenosine triphosphate (eATP). We report that activation of the Nlrp3 inflammasome increases autocrine release of eATP, which promotes incorporation of the CXCR4 receptor into membrane lipid rafts at the leading surface of migrating cells. On the other hand, a lack of Nlrp3 inflammasome expression in BM conditioned for transplantation leads to a decrease in expression of SDF-1 and dangerassociated molecular pattern molecules (DAMPs), which are responsible for activation of the complement cascade (ComC), which in turn facilitates the homing and engraftment of HSPCs. Keywords Nlrp3 inflammasome . Purinergic signaling . Extracellular nucleotides . Complement cascade . Stem cell homing . Stem cell engraftment . Bone marrow sterile inflammation Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12015-020-10005-w) contains supplementary material, which is available to authorized users. * Mariusz Z. Ratajczak [email protected]
Janina Ratajczak [email protected]
Mateusz Adamiak [email protected] Ahmed Abdel-Latif [email protected] Kamila Bujko [email protected]
Magda Kucia [email protected] 1
Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY 40202, USA
2
Center for Preclinical Studies and Technology, Department of Regenerative Medicine at, Medical University of Warsaw, Warsaw, Poland
3
Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, USA
4
Institute of Veterinary Medicine, Department of Food Hygiene and Public Health Protection, Warsaw University of Life Sciences (WULS-SGGW), Warsaw, Poland
5
Department of Hematology, University of Zielona Gora, Hospital Gorzow Wlkp, Zielona Góra, Poland
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