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SHR Neuro Krebs Kardio Lipid

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 [OPEN ACCESS]
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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 -

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