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10.1038/emboj.2009.163
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Título: | Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1beta release through pyrophosphates |
Fecha de publicación: | 2009 |
Editorial: | EMBO Press |
Cita bibliográfica: | EMBO Journal, volumen 28, nº 14, año 2009, páginas 2114-2127. |
ISSN: | 1460-2075 0261-4189 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas |
Palabras clave: | Macrófagos NLRP3 Inflammasoma Inflamación Caspasa-1 |
Resumen: | In acute inflammation extracellular ATP activates P2X7 ion channel receptors (P2X7R) on M1 polarized macrophages to release pro-inflammatory IL-1bvia activation of the caspase-1/Nucleotide-binding domain and Leucine-rich repeat receptor containing Pyrin domain 3 (NLRP3) inflammasome. In contrast, M2 polarized macrophages are critical to the resolution of inflammation but neither actions of P2X7R on these macrophages, nor mechanisms by which macrophages switch from pro-inflammatory to anti-inflammatory phenotypes, are known. Here we investigated extracellular ATP signaling over a dynamic macrophage polarity gradient from M1 through M2 phenotypes. In macrophages polarized towards, but not at, M2 phenotype, where intracellular IL-1b remains high and the inflammasome is intact, P2X7R activation selectively uncouples to the NLRP3-inflammasome activation but not to upstream ion channel activation. In these intermediate M1/M2 polarized macrophages, extracellular ATP now acts via its pyrophosphate chains, independently of other purine receptors, to inhibit IL-1b release by other stimuli via two independent mechanisms: inhibition of ROS production and trapping of the inflammasome complex via intracellular clustering of actin filaments. |
Autor/es principal/es: | Pelegrin, Pablo Surprenant, Annmarie |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular B e Inmunología |
Versión del editor: | https://www.embopress.org/doi/full/10.1038/emboj.2009.163?pubCode=cgi |
URI: | http://hdl.handle.net/10201/137735 |
DOI: | 10.1038/emboj.2009.163 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 46 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Descripción: | ©2009. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in The EMBO Journal. To access the final edited and published work see https://doi.org/10.1038/emboj.2009.163 |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
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