STAT5 is an ambivalent regulator of neutrophil homeostasis
| Autor: | Bernard Pajak, Alain Vanderplasschen, Oberdan Leo, Fabrice Bureau, Virginie Garzé, Laurence Fievez, Françoise Bex, Philippe Boutet, Muriel Moser, Percy A. Knolle, Silke Hegenbarth, Emmanuelle Henry, Pierre Lekeux, Fabrice Jaspar, Laurent Gillet, Christophe Desmet |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Neutrophils
lcsh:Medicine Inflammation Biology Granulopoiesis Cell Biology/Cell Signaling Mice Immunology/Leukocyte Signaling and Gene Expression hemic and lymphatic diseases Granulocyte Colony-Stimulating Factor STAT5 Transcription Factor medicine Animals Homeostasis Cell Lineage Progenitor cell Neutrophil homeostasis lcsh:Science Cells Cultured Mice Knockout Multidisciplinary Stem Cells lcsh:R Endothelial Cells Sciences bio-médicales et agricoles Neutrophilia Cell biology Mice Inbred C57BL Haematopoiesis Liver Immunology Cytokines Female lcsh:Q Stromal Cells Stem cell medicine.symptom Granulocytes Research Article |
| Zdroj: | PLoS ONE, Vol 2, Iss 8, p e727 (2007) PloS one, 2 (1 PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND: Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that in STAT5-/- mice, liver endothelial cells (LECs) autonomously secrete high amounts of G-CSF, allowing myeloid progenitors to overcompensate for their intrinsic survival defect. However, when injected with pro-inflammatory cytokines, mutant mice cannot further increase neutrophil production, display a severe deficiency in peripheral neutrophil survival, and are therefore unable to maintain neutrophil homeostasis. In wild-type mice, inflammatory stimulation induces rapid STAT5 degradation in LECs, G-CSF production by LECs and other cell types, and then sustained mobilization and expansion of long-lived neutrophils. CONCLUSION: We conclude that STAT5 is an ambivalent factor. In cells of the granulocytic lineage, it exerts an antiapoptotic function that is required for maintenance of neutrophil homeostasis, especially during the inflammatory response. In LECs, STAT5 negatively regulates granulopoiesis by directly or indirectly repressing G-CSF expression. Removal of this STAT5-imposed brake contributes to induction of emergency granulopoiesis. Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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