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Boettcher, S.* ; Gerosa, R.* ; Radpour, R.* ; Bauer, J. ; Ampenberger, F.* ; Heikenwälder, M. ; Kopf, M.* ; Manz, M.G.*

Endothelial cells translate pathogen signals into G-CSF-driven emergency granulopoiesis.

Blood 124, 1393-1403 (2014)
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Systemic bacterial infection induces a hematopoietic response program termed 'emergency granulopoiesis' that is characterized by increased de novo bone marrow (BM) neutrophil production. How loss of local immune control and bacterial dissemination is sensed and subsequently translated into the switch from steady-state to emergency granulopoiesis is, however, unknown. Using tissue-specific myeloid differentiation primary response gene 88 (Myd88)-deficient mice and in vivo lipopolysaccharide (LPS) administration to model severe bacterial infection, we here show that endothelial cells (ECs) but not hematopoietic cells, hepatocytes, pericytes or bone marrow stromal cells, are essential cells for this process. Indeed, ECs from multiple tissues including BM express high levels of Tlr4 and Myd88, and are the primary source of granulocyte colony-stimulating factor (G-CSF), the key granulopoietic cytokine, following LPS challenge or infection with E. coli. Endothelial cell-intrinsic MYD88-signaling and subsequent G-CSF production by ECs is required for myeloid progenitor lineage skewing towards granulocyte-macrophage progenitors (GMPs), increased colony-forming unit granulocyte (CFU-G) activity in BM, and accelerated BM neutrophil generation following LPS stimulation. Thus, ECs catalyze the detection of systemic infection into demand-adapted granulopoiesis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Colony-stimulating Factor; Hematopoietic Stem-cells; Toll-like Receptors; Bone-marrow Niche; Progenitor Cells; Deficient Mice; Adhesion Molecule-1; Innate Immunity; Human-monocytes; Granulocyte
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 124, Issue: 9, Pages: 1393-1403 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place Washington
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-551600-001
PubMed ID 24990886
DOI 10.1182/blood-2014-04-570762
WOS ID WOS:000342762100011
Erfassungsdatum 2014-07-07
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