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

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.

Isolation and Phenotyping of Bone Marrow Macrophages.

Macrophages are present in most of the tissues in the organism. They are basically separated into two categories: the resident macrophages, specific of the tissue and capable of proliferation, and the macrophages deriving from the monocyte differentiation. In the bone marrow, the "resident" macrophages are part of the hematopoietic stem cell niche.