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Article Dans Une Revue Blood Advances Année : 2022

Deleterious effect of bone marrow-resident macrophages on hematopoietic stem cells in response to total body irradiation

Résumé

Abstract Bone marrow (BM) resident macrophages interact with a population of long-term hematopoietic stem cells (LT-HSCs) 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-HSCs is associated with increased percentages of LT-HSCs with reactive oxygen species (ROS) and of BM resident macrophages producing nitric oxide (NO), resulting in an increased percentage of LT-HSCs with endogenous cytotoxic peroxynitrites. Pharmacological or genetic depletion of BM resident macrophages impairs the radio-induced increases in the percentage of both ROS+ LT-HSCs and peroxynitrite+ LT-HSCs and results in a complete recovery of a functional pool of LT-HSCs. Finally, we show that after a 2 Gy-TBI, a specific decrease of NO production by BM resident macrophages improves the LT-HSC recovery, whereas an exogenous NO delivery decreases the LT-HSC compartment. Altogether, these results show that BM resident macrophages are involved in the response of LT-HSCs 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-HSCs.

Dates et versions

hal-04251517 , version 1 (20-10-2023)

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Citer

Marion Chalot, Vilma Barroca, Saiyirami Devanand, Françoise Hoffschir, Paul-Henri Romeo, et al.. Deleterious effect of bone marrow-resident macrophages on hematopoietic stem cells in response to total body irradiation. Blood Advances, 2022, 6 (6), pp.1766-1779. ⟨10.1182/bloodadvances.2021005983⟩. ⟨hal-04251517⟩
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