| First Author | Chalot M | Year | 2022 |
| Journal | Blood Adv | Volume | 6 |
| Issue | 6 | Pages | 1766-1779 |
| PubMed ID | 35100346 | Mgi Jnum | J:334685 |
| Mgi Id | MGI:7461988 | Doi | 10.1182/bloodadvances.2021005983 |
| Citation | Chalot M, et al. (2022) Deleterious effect of bone marrow-resident macrophages on hematopoietic stem cells in response to total body irradiation. Blood Adv 6(6):1766-1779 |
| abstractText | 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. |
