Novel Evidence That Alternative Pathway of Complement Cascade Activation is Required for Optimal Homing and Engraftment of Hematopoietic Stem/progenitor Cells.
Engraftment
Factor B
Nlrp3 inflammasome
Proteomics
Stem cell homing
The alternative pathway of the complement cascade
Journal
Stem cell reviews and reports
ISSN: 2629-3277
Titre abrégé: Stem Cell Rev Rep
Pays: United States
ID NLM: 101752767
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
accepted:
09
12
2021
pubmed:
12
1
2022
medline:
27
4
2022
entrez:
11
1
2022
Statut:
ppublish
Résumé
We reported in the past that activation of the third (C3) and fifth element (C5) of complement cascade (ComC) is required for a proper homing and engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs). Since myeloablative conditioning for transplantation triggers in recipient bone marrow (BM) state of sterile inflammation, we have become interested in the role of complement in this process and the potential involvement of alternative pathway of ComC activation. We noticed that factor B deficient mice (FB-KO) that do not activate properly alternative pathway, engraft poorly with BM cells from normal wild type (WT) mice. We observed defects both in homing and engraftment of transplanted HSPCs. To shed more light on these phenomena, we found that myeloablative lethal irradiation conditioning for transplantation activates purinergic signaling, ComC, and Nlrp3 inflammasome in WT mice, which is significantly impaired in FB-KO animals. Our proteomics analysis revealed that conditioned for transplantation lethally irradiated FB-KO compared to normal control animals have lower expression of several proteins involved in positive regulation of cell migration, trans-endothelial migration, immune system, cellular signaling protein, and metabolic pathways. Overall, our recent study further supports the role of innate immunity in homing and engraftment of HSPCs.
Identifiants
pubmed: 35013937
doi: 10.1007/s12015-021-10318-4
pii: 10.1007/s12015-021-10318-4
pmc: PMC9033710
doi:
Substances chimiques
Inflammasomes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1355-1365Subventions
Organisme : NIDDK NIH HHS
ID : 2R01 DK074720
Pays : United States
Informations de copyright
© 2022. The Author(s).
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