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Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis

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Sánchez, Ángela & Relaño, Carlos & Carrasco, Araceli & Contreras Jurado, Silvia Constanza & Martín Duce, Antonio & Aranda, Ana & Alemany, Susana .Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis.

ISO 690

Sánchez, Ángela & Relaño, Carlos & Carrasco, Araceli & Contreras Jurado, Silvia Constanza & Martín Duce, Antonio & Aranda, Ana & Alemany, Susana. Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis.

https://hdl.handle.net/20.500.12080/26183
dc.contributor.author Sánchez, Ángela
dc.contributor.author Relaño, Carlos
dc.contributor.author Carrasco, Araceli
dc.contributor.author Contreras Jurado, Silvia Constanza
dc.contributor.author Martín Duce, Antonio
dc.contributor.author Aranda, Ana
dc.contributor.author Alemany, Susana
dc.date.accessioned 2021-11-10T15:25:09Z
dc.date.available 2021-11-10T15:25:09Z
dc.date.created 2017-07-17
dc.identifier.uri https://hdl.handle.net/20.500.12080/26183
dc.description.abstract Map3k8 has been proposed as a useful target for the treatment of inflammatory diseases. We show here that during lipopolysaccharide-induced emergency granulopoiesis, Map3k8 deficiency strongly impairs the increase in circulating mature (Ly6GhighCD11b+) and immature (Ly6GlowCD11b+) neutrophils. After chimaeric bone marrow (BM) transplantation into recipient Map3k8¿/¿ mice, lipopolysaccharide treatment did not increase circulating Ly6GhighCD11b+ cells and strongly decreased circulating Ly6GlowCD11b+ cells. Lipopolysaccharide-treated Map3k8¿/¿ mice showed decreased production of granulocyte colony-stimulating factor (G-CSF), a key factor in neutrophil expansion, and a Map3k8 inhibitor blocked lipopolysaccharide-mediated G-CSF expression in endothelial cell lines. Ly6GlowCD11b+ BM cells from lipopolysaccharide-treated Map3k8¿/¿ mice displayed impaired expression of CCAAT-enhancer-binding protein ¿, which depends on G-CSF for expression and is crucial for cell cycle acceleration in this life-threatening condition. Accordingly, lipopolysaccharide-treated Map3k8¿/¿ mice showed decreased Ly6GlowCD11b+ BM cell proliferation, as evidenced by a decrease in the percentage of the most immature precursors, which have the highest proliferation capacity among this cell population. Thus, Map3k8 expression by non-haematopoietic tissue is required for lipopolysaccharide-induced emergency granulopoiesis. The novel observation that inhibition of Map3k8 activity decreases neutrophilia during life-threatening systemic infection suggests a possible risk in the proposed use of Map3k8 blockade as an anti-inflammatory therapy. es_ES
dc.format application/pdf es_ES
dc.language eng es_ES
dc.rights CC-BY es_ES
dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.es es_ES
dc.title Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


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