title: Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process.
abstract: The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released after P2X7R stimulation goes beyond caspase-1 secretome. The characterization of P2X7R-secretome reveals a new function of this receptor through a fine-tuning of protein release. We found that P2X7R stimulation in macrophages is able to release potent anti-inflammatory proteins, such as Annexin A1, independently of their polarization state suggesting for first time a potential role for P2X7R during resolution of the inflammation and not linked to the release of pro-inflammatory cytokines. These results are of prime importance for the development of therapeutics targeting P2X7R.
authors.affiliation: Inflammation and Experimental Surgery Unit, CIBERehd, Murcia's BioHealth Research Institute IMIB-Arrixaca, Clinical University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: de Torre-Minguela
authors.affiliation: Inflammation and Experimental Surgery Unit, CIBERehd, Murcia's BioHealth Research Institute IMIB-Arrixaca, Clinical University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Barberà-Cremades
authors.affiliation: Inflammation and Experimental Surgery Unit, CIBERehd, Murcia's BioHealth Research Institute IMIB-Arrixaca, Clinical University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Gómez
authors.affiliation: Inflammation and Experimental Surgery Unit, CIBERehd, Murcia's BioHealth Research Institute IMIB-Arrixaca, Clinical University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Martín-Sánchez
authors.affiliation: Inflammation and Experimental Surgery Unit, CIBERehd, Murcia's BioHealth Research Institute IMIB-Arrixaca, Clinical University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Pelegrín
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000276:immunology*; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology*
chemical_list: D017305:Annexin A1; D058486:Receptors, Purinergic P2X7; C573274:annexin A1, mouse; D020170:Caspase 1