Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1beta release through pyrophosphates

Pelegrin, Pablo; Surprenant, Annmarie

Publication:
Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1beta release through pyrophosphates

dc.contributor.author	Pelegrin, Pablo
dc.contributor.author	Surprenant, Annmarie
dc.contributor.department	Bioquímica y Biología Molecular B e Inmunología
dc.date.accessioned	2024-01-25T09:33:06Z
dc.date.available	2024-01-25T09:33:06Z
dc.date.issued	2009
dc.description	©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	es
dc.description.abstract	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.	es
dc.format	application/pdf	es
dc.format.extent	46	es
dc.identifier.citation	EMBO Journal, volumen 28, nº 14, año 2009, páginas 2114-2127.
dc.identifier.doi	10.1038/emboj.2009.163
dc.identifier.issn	1460-2075
dc.identifier.issn	0261-4189
dc.identifier.uri	http://hdl.handle.net/10201/137735
dc.language	eng	es
dc.publisher	EMBO Press	es
dc.relation	Wellcome Trust	es
dc.relation.publisherversion	https://www.embopress.org/doi/full/10.1038/emboj.2009.163?pubCode=cgi	es
dc.rights	info:eu-repo/semantics/openAccess	es
dc.rights	Attribution-NonCommercial-NoDerivatives 4.0 Internacional	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject	Macrófagos	es
dc.subject	NLRP3	es
dc.subject	Inflammasoma	es
dc.subject	Inflamación	es
dc.subject	Caspasa-1	es
dc.subject.other	CDU::6 - Ciencias aplicadas	es
dc.title	Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1beta release through pyrophosphates	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es