Abstract
In the bone marrow (BM) hematopoietic niche, the oxygen tension is usually very low. Such condition affects stem and progenitor cell proliferation and differentiation and, at cellular level regulates hematopoietic growth factors, chemokines and adhesion molecules expression. In turn, these molecules affect the proliferation and maturation of other cellular components of the niche. Due to the complexity of the system we started the in vitro investigations of the IL-6, IL-8, TNFα cytokines expression and the vascular endothelial growth factor (VEGF), considered key mediators of the hematopoietic niche, in human macrophages and macrophage cell line. Since in the niche the oxygen availability is mediated by red blood cells (RBCs), we have influenced the anoxic cell cultures by the administration of oxygenated or deoxygenated RBCs (deoxy RBCs). The results reported in this brief paper show that the presence of RBCs up-regulates IL-8 mRNA while IL-6 and VEGF mRNA expression appears down-regulated. This does not occur when deoxy RBCs are used. Moreover, it appears that the administration of RBCs leads to an increase of TNFα expression levels in MonoMac 6 (MM6). Interestingly, the modulation of these factors likely occurs in a hypoxia-inducible factor-1α (HIF-1α) independent manner. Considering the role of oxygen in the hematopoietic niche further studies should explore these preliminary observations in more details.
Highlights
The bone marrow (BM) is a tissue of complex architecture that is organized into a hematopoietic cell compartment and the stroma, which is mainly composed of fibroblasts, adipocytes, nerves, and the BM’s vascular system (Morrison and Scadden, 2014; Tamma and Ribatti, 2017)
Some studies have already shown that HIFs, but not NF-kB, are important transcriptional effectors regulating the responses of macrophages exposed to 18 h hypoxia (Fang et al, 2009)
The results were compared to those obtained with the chemical agent CoCl2 which has been shown to mimic the hypoxic conditions in cells by stabilizing the transcription factor hypoxia-inducible factor-1α (HIF-1α)
Summary
The bone marrow (BM) is a tissue of complex architecture that is organized into a hematopoietic cell compartment and the stroma, which is mainly composed of fibroblasts, adipocytes, nerves, and the BM’s vascular system (Morrison and Scadden, 2014; Tamma and Ribatti, 2017). In BM thin-walled sinusoidal vessels are highly specialized capillaries with a discontinuous basement membrane and fenestrations that facilitate trafficking of cells and soluble factors between the blood and the BM compartment. This vasculature provides a route for mature hematopoietic cells to the peripheral circulation and a place where hematopoietic progenitors differentiate and set the stage for full reconstitution of hematopoiesis, which maintains in the peripheral blood a constant level of the different blood cell types and components (erythrocytes granulocytes, platelets, lymphocytes, etc.). Previous studies have suggested that local oxygen tension determines the location of hematopoietic stem cells (HSCs) in the BM compartment (Parmar et al, 2007; Spencer et al, 2014)
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