ABSTRACT
BACKGROUND & AIMS: Protein malnutrition (PM) affects hematopoiesis leading to bone marrow (BM) hypoplasia and arrests hematopoietic stem cells (HSC) in G0/G1 cell cycle phases, which cause anemia and leukopenia. Hematopoiesis is mainly regulated by BM niches where endothelial cells (EC) present a key regulatory role. Thus, our objective is to evaluate whether PM affects the modulatory capacity of EC on hematopoiesis. METHODS: C57BL/6 male mice received for 5 weeks a normal protein diet (12% casein) or a low protein diet (2% casein). MSC were isolated and differentiated in vitro into EC and the synthesis of SCF, Ang-1, CXCL-12, IL-11, TGF-ß and G-CSF were evaluated. The HSC and hematopoietic progenitors were quantified and the EC capacity to modulate the hematopoietic system was also evaluated. Moreover, the ability of PM bone marrow to support hematopoieisis was assessed by proliferation of infused leukemic myelo-monoblasts cells. RESULTS: PM decreases HSC and hematopoietic progenitor pool and promotes cell cycle arrest and a lower proliferation rate of leukemic myelo-monoblasts. PM also committed hematopoietic regulatory characteristics from EC, resulting in the modification of both cell cycle pattern and hematopoietic differentiation. CONCLUSION: BM microenvironment is compromised in PM, and since PM disturbs EC, it becomes one of the factors responsible for the hematopoietic cell cycle arrest and impairment of HSC differentiation.
Subject(s)
Bone Marrow Cells/drug effects , Dietary Proteins/pharmacology , Endothelial Cells/drug effects , Endothelial Cells/physiology , Hematopoiesis/drug effects , Protein Deficiency , Anemia , Animal Nutritional Physiological Phenomena , Animals , Cell Differentiation , Cell Line , Coculture Techniques , Diet , Leukopenia , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/physiology , Mice , Mice, Inbred C57BLABSTRACT
The immune system is essential for the control and elimination of infections, and macrophages are cells that act as important players in orchestrating the various parts of the inflammatory/immune response. Amino acids play important role in mediating functionality of the inflammatory response, especially mediating macrophages functions and cytokines production. We investigated the influence of glutamine, taurine and their association on the modulation of inflammatory pathway markers in macrophages. The RAW 264.7 macrophage cell line was cultivated in the presence of glutamine and taurine and proliferation rates, cell viability, cell cycle phases, IL-1α, IL-6, IL-10 and TNF-α as well as H2O2 production and the expression of the transcription factor, NFκB, and its inhibitor, IκBα, were evaluated. Our results showed an increase in viable cells and increased proliferation rates of cells treated with glutamine concentrations over 2 mM, as well as cells treated with both glutamine and taurine. The cell cycle showed a higher percentage of cells in the phases S, G2 and M when they were treated with 2 or 10 mM glutamine, or with glutamine and taurine in cells stimulated with lipopolysaccharide. The pNFκB/NFκB showed reduced ratio expression when cells were treated with 10 mM of glutamine or with glutamine in association with taurine. These conditions also resulted in reduced TNF-α, IL-1α and H2O2 production, and higher production of IL-10. These findings demonstrate that glutamine and taurine are able to modulate macrophages inflammatory pathways, and that taurine can potentiate the effects of glutamine, illustrating their immunomodulatory properties.
