SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells
Hay una corrección posterior a este artículo disponible en http://hdl.handle.net/10486/715274
| Autores: | , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/710124 |
| Acceso en línea: | http://hdl.handle.net/10486/710124 https://dx.doi.org/10.1186/s12964-023-01397-6 |
| Access Level: | acceso abierto |
| Palabra clave: | NLRP3 inflammasome SARS-CoV-2 blood coagulation factors endothelial cells monocytes Farmacia |
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SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cellsVillacampa Calvo, AliciaAlfaro, EnriqueMorales, CristinaDíaz García, ElenaLópez-Fernández, CristinaBartha Rasero, José LuisLópez-Sánchez, FranciscoLorenzo González, ÓscarMoncada, SalvadorSánchez Ferrer, Carlos FélixGarcía Río, FranciscoCubillos Zapata, CarolinaPeiró Vallejo, M. ConcepciónNLRP3 inflammasomeSARS-CoV-2blood coagulation factorsendothelial cellsmonocytesFarmaciaHay una corrección posterior a este artículo disponible en http://hdl.handle.net/10486/715274Background: Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. Methods: In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results: S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1β formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1β. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. Conclusion: S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video AbstractSupported by funds from REACT-EU-Comunidad de Madrid and the European Regional Development Fund (SPACE2-CV-COVID-CM) to C. Peiró and O. Lorenzo, Fondo de Investigación Sanitaria-FIS Carlos III (PI20/00923) to O. Lorenzo, Plan Nacional I + D (PID2020-115590RB-100/AEI/ https:// doi. org/ 10. 13039/ 50110 00110 33) to C. Peiró and C.F. Sánchez-Ferrer, Instituto de Salud Carlos III PI19/01612, PI22/01262 to F. García-Río and CP18/0028, PI19/01363 and PI22/01257 to C. Cubillos-ZapataBMCDepartamento de FarmacologíaFacultad de Medicina20242024-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/710124https://dx.doi.org/10.1186/s12964-023-01397-6reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7101242026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells |
| title |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells |
| spellingShingle |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells Villacampa Calvo, Alicia NLRP3 inflammasome SARS-CoV-2 blood coagulation factors endothelial cells monocytes Farmacia |
| title_short |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells |
| title_full |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells |
| title_fullStr |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells |
| title_full_unstemmed |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells |
| title_sort |
SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells |
| dc.creator.none.fl_str_mv |
Villacampa Calvo, Alicia Alfaro, Enrique Morales, Cristina Díaz García, Elena López-Fernández, Cristina Bartha Rasero, José Luis López-Sánchez, Francisco Lorenzo González, Óscar Moncada, Salvador Sánchez Ferrer, Carlos Félix García Río, Francisco Cubillos Zapata, Carolina Peiró Vallejo, M. Concepción |
| author |
Villacampa Calvo, Alicia |
| author_facet |
Villacampa Calvo, Alicia Alfaro, Enrique Morales, Cristina Díaz García, Elena López-Fernández, Cristina Bartha Rasero, José Luis López-Sánchez, Francisco Lorenzo González, Óscar Moncada, Salvador Sánchez Ferrer, Carlos Félix García Río, Francisco Cubillos Zapata, Carolina Peiró Vallejo, M. Concepción |
| author_role |
author |
| author2 |
Alfaro, Enrique Morales, Cristina Díaz García, Elena López-Fernández, Cristina Bartha Rasero, José Luis López-Sánchez, Francisco Lorenzo González, Óscar Moncada, Salvador Sánchez Ferrer, Carlos Félix García Río, Francisco Cubillos Zapata, Carolina Peiró Vallejo, M. Concepción |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Farmacología Facultad de Medicina |
| dc.subject.none.fl_str_mv |
NLRP3 inflammasome SARS-CoV-2 blood coagulation factors endothelial cells monocytes Farmacia |
| topic |
NLRP3 inflammasome SARS-CoV-2 blood coagulation factors endothelial cells monocytes Farmacia |
| description |
Hay una corrección posterior a este artículo disponible en http://hdl.handle.net/10486/715274 |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024-01-01 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/710124 https://dx.doi.org/10.1186/s12964-023-01397-6 |
| url |
http://hdl.handle.net/10486/710124 https://dx.doi.org/10.1186/s12964-023-01397-6 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
BMC |
| publisher.none.fl_str_mv |
BMC |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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