Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Taschner, S; Koesters, C; Platzer, B; Jörgl, A; Ellmeier, W; Benesch, T; Strobl, H.
Down-regulation of RXRalpha expression is essential for neutrophil development from granulocyte/monocyte progenitors.
Blood. 2007; 109(3):971-979
Doi: 10.1182/blood-2006-04-020552
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- Führende Autor*innen der Med Uni Graz
- Strobl Herbert
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- Abstract:
- Neutrophil granulocytes (Gs) represent highly abundant and short-lived leukocytes that are constantly regenerated from a small pool of myeloid committed progenitors. Nuclear receptor (NR) family members are ligand-activated transcription factors that play key roles in cellular proliferation and differentiation processes including myelopoiesis. Retinoid X receptor alpha (RXRalpha) represents the predominant NR types I and II homo- and heterodimerization partner in myeloid cells. Here we show that human myeloid progenitors express RXRalpha protein at sustained high levels during macrophage colony-stimulating factor (M-CSF)-induced monopoiesis. In sharp contrast, RXRalpha is down-regulated during G-CSF-dependent late-stage neutrophil differentiation from myeloid progenitors. Down-regulation of RXRalpha is critically required for neutrophil development since ectopic RXRalpha inhibited granulopoiesis by impairing proliferation and differentiation. Moreover, ectopic RXRalpha was sufficient to redirect G-CSF-dependent granulocyte differentiation to the monocyte lineage and to promote M-CSF-induced monopoiesis. Functional genetic interference with RXRalpha signaling in hematopoietic progenitor/stem cells using a dominant-negative RXRalpha promoted the generation of late-stage granulocytes in human cultures in vitro and in reconstituted mice in vivo. Therefore, our data suggest that RXRalpha down-regulation is a critical requirement for the generation of neutrophil granulocytes.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Differentiation - drug effects
- Cell Lineage - drug effects
- Cell Proliferation -
- Cells, Cultured -
- Down-Regulation - genetics
- Humans -
- Macrophage Colony-Stimulating Factor - pharmacology
- Mice -
- Myeloid Progenitor Cells - cytology
- Myelopoiesis - drug effects
- Neutrophils - cytology
- Retinoid X Receptor alpha - genetics
- Transduction, Genetic -