Danger-associated molecular pattern molecules take unexpectedly a central stage in Nlrp3 inflammasome-caspase-1-mediated trafficking of hematopoietic stem/progenitor cells
Autor: | Kamila Bujko, Janina Ratajczak, Arjun Thapa, Mateusz Adamiak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak |
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Rok vydání: | 2020 |
Předmět: |
Damp
Cancer Research Haematopoietic system Inflammasomes Interleukin-1beta Caspase 1 Stem cells Article Mice Cell Movement Granulocyte Colony-Stimulating Factor NLR Family Pyrin Domain-Containing 3 Protein medicine Alarmins Animals Progenitor cell Inflammation Mice Knockout Chemistry Haematopoietic stem cells Hematopoietic Stem Cell Transplantation Inflammasome Hematology Hematopoietic Stem Cells Hematopoietic Stem Cell Mobilization Cell biology Transplantation Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure Oncology Female Bone marrow Homing (hematopoietic) medicine.drug |
Zdroj: | Leukemia |
ISSN: | 1476-5551 |
Popis: | Like their homing after transplantation to bone marrow (BM), the mobilization of hematopoietic stem/progenitor cells (HSPCs) is still not fully understood, and several overlapping pathways are involved. Several years ago our group proposed that sterile inflammation in the BM microenvironment induced by pro-mobilizing agents is a driving force in this process. In favor of our proposal, both complement cascade (ComC)-deficient and Nlrp3 inflammasome-deficient mice are poor G-CSF and AMD3100 mobilizers. It is also known that the Nlrp3 inflammasome mediates its effects by activating caspase-1, which is responsible for proteolytic activation of interleukin-1β (IL-1β) and interleukin-18 (IL-18) and their release from cells along with several danger-associated molecular pattern molecules (DAMPs). We observed in the past that IL-1β and IL-18 independently promote mobilization of HSPCs. In the current work we demonstrated that caspase-1-KO mice are poor mobilizers, and, to our surprise, administration of IL-1β or IL-18, as in the case of Nlrp3-KO animals, does not correct this defect. Moreover, neither Caspase-1-KO nor Nlrp3-KO mice properly activated the ComC to execute the mobilization process. Interestingly, mobilization in these animals and activation of the ComC were both restored after injection of the DAMP cocktail eATP+HGMB1+S100A9, the components of which are normally released from cells in an Nlrp3 inflammasome–caspase-1-dependent manner. In addition, we report that caspase-1-deficient HSPCs show a decrease in migration in response to BM homing factors and engraft more poorly after transplantation. These results for the first time identify caspase-1 as an orchestrator of HSPC trafficking. |
Databáze: | OpenAIRE |
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