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IFNα-mediated remodeling of endothelial cells in the bone marrow niche

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Item Type:Article
Title:IFNα-mediated remodeling of endothelial cells in the bone marrow niche
Creators Name:Prendergast, Á.M. and Kuck, A. and van Essen, M. and Haas, S. and Blaszkiewicz, S. and Essers, M.A.G.
Abstract:In the bone marrow, endothelial cells are a major component of the hematopoietic stem cell vascular niche and are a first line of defense against inflammatory stress and infection. The primary response of an organism to infection involves the synthesis of immune-modulatory cytokines, including interferon alpha. In the bone marrow, interferon alpha induces rapid cell cycle entry of hematopoietic stem cells in vivo. However, the effect of interferon alpha on bone marrow endothelial cells has not been described. Here, we demonstrate that acute interferon alpha treatment leads to rapid stimulation of bone marrow endothelial cells in vivo, resulting in increased bone marrow vascularity and vascular leakage. We find that activation of bone marrow endothelial cells involves the expression of key inflammatory and endothelial cell-stimulatory markers. This interferon alpha-mediated activation of bone marrow endothelial cells is dependent in part on vascular endothelial growth factor signaling in bone marrow hematopoietic cell types, including hematopoietic stem cells. Thus, this implies a role for hematopoietic stem cells in remodeling of the bone marrow niche in vivo following inflammatory stress. These data increase our current understanding of the relationship between hematopoietic stem cells and the bone marrow niche under inflammatory stress and also clarify the response of bone marrow niche endothelial cells to acute interferon alpha treatment in vivo.
Keywords:Biological Models, Biomarkers, Bone Marrow, Bone Marrow Cells, Capillary Permeability, Cell Proliferation, Cellular Microenvironment, Endothelial Cells, Hematopoiesis, Hematopoietic Stem Cells, Immunophenotyping, Interferon-alpha, Knockout Mice, Phenotype, Physiologic Neovascularization, Physiological Stress, Poly I-C, Signal Transduction, Stem Cell Niche, Vascular Endothelial Growth Factor A, Animals, Mice
Publisher:Ferrata Storti Foundation
Page Range:445-453
Date:March 2017
Official Publication:https://doi.org/10.3324/haematol.2016.151209
PubMed:View item in PubMed

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