title: IFNα-mediated remodeling of endothelial cells in the bone marrow niche.
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 cellsin vivoHowever, 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 cellsin 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 nichein vivofollowing 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 treatmentin vivo.
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Deutsches Krebsforschungszentrum, Heidelberg, Germany.|Hematopoietic Stem Cells and Stress Group, Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Áine M
authors.initials: ÁM
authors.lastname: Prendergast
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Deutsches Krebsforschungszentrum, Heidelberg, Germany.|Hematopoietic Stem Cells and Stress Group, Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuck
authors.affiliation: Hematopoietic Stem Cells and Stress Group, Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Mieke
authors.initials: M
authors.lastname: van Essen
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Deutsches Krebsforschungszentrum, Heidelberg, Germany.|Hematopoietic Stem Cells and Stress Group, Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Haas
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Deutsches Krebsforschungszentrum, Heidelberg, Germany.|Hematopoietic Stem Cells and Stress Group, Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Blaszkiewicz
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Deutsches Krebsforschungszentrum, Heidelberg, Germany m.essers@dkfz.de.|Hematopoietic Stem Cells and Stress Group, Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Marieke A G
authors.initials: MA
authors.lastname: Essers
mesh_terms: D000818:Animals; D015415:Biomarkers; D001853:Bone Marrow / Q000098:blood supply / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002199:Capillary Permeability; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D055153:Stem Cell Niche; D013312:Stress, Physiological; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D016898:Interferon-alpha; D042461:Vascular Endothelial Growth Factor A; D011070:Poly I-C