RRC ID 69475
Author Chalot M, Barroca V, Devanand S, Hoffschir F, Romeo PH, Moreno SG.
Title Deleterious effect of bone marrow-resident macrophages on hematopoietic stem cells in response to total body irradiation.
Journal Blood Adv
Abstract Bone marrow resident macrophages interact with a population of long-term hematopoietic stem cell (LT-HSC) but their role on LT-HSC properties after stress is not well defined. Here, we show that a 2 Gy total body irradiation (TBI)-mediated death of LT-HSC is associated with increased percentages of LT-HSC with reactive oxygen species (ROS) and of bone marrow resident macrophages producing nitric oxide (NO), resulting in an increased percentage of LT-HSC with endogenous cytotoxic peroxynitrites. Pharmacological or genetic depletion of bone marrow resident macrophages impairs the radio-induced increases in the percentage of both ROS+ LT-HSC and peroxynitrite+ LT-HSC and results in a complete recovery of a functional pool of LT-HSC. Finally, we show that after a 2 Gy-TBI, a specific decrease of NO production by bone marrow resident macrophages improves the LT-HSC recovery, whereas an exogenous NO delivery decreases the LT-HSC compartment. Altogether, these results show that bone marrow resident macrophages are involved in the response of LT-HSC to a 2 Gy-TBI and suggest that regulation of NO production can be used to modulate some deleterious effects of a TBI on LT-HSC.
Volume 6(6)
Pages 1766-1779
Published 2022-3-22
DOI 10.1182/bloodadvances.2021005983
PII 483749
PMID 35100346
PMC PMC8941479
MeSH Bone Marrow* Hematopoietic Stem Cells Macrophages Reactive Oxygen Species Whole-Body Irradiation* / adverse effects
IF 4.91
Mice RBRC04395