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Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantation

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dc.contributor.authorLucas-Ruiz, Fernando
dc.contributor.authorMateo, Sandra V.
dc.contributor.authorJover-Aguilar, Marta
dc.contributor.authorAlconchel, Felipe
dc.contributor.authorMartínez-Alarcón, Laura
dc.contributor.authorTorre-Minguela, Carlos de
dc.contributor.authorVidal-Correoso, Daniel
dc.contributor.authorVillalva-López, Francisco
dc.contributor.authorLópez-López, Víctor
dc.contributor.authorRios-Zambudio, Antonio
dc.contributor.authorPons Miñano, José Antonio
dc.contributor.authorRamírez, Pablo
dc.contributor.authorBaroja-Mazo, Alberto
dc.contributor.authorPelegrín Vivancos, Pablo
dc.contributor.departmentMedicina
dc.date.accessioned2025-01-26T11:00:07Z
dc.date.available2025-01-26T11:00:07Z
dc.date.issued2022-12-19
dc.description© 2022 The Author(s). 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 Published version of a Published Work that appeared in final form in EBioMedicine. To access the final edited and published work see https://doi.org/10. 1016/j.ebiom.2022. 104419
dc.description.abstractBackground Innate immunity plays a fundamental role in solid organ transplantation. Myeloid cells can sense danger signals or DAMPs released after tissue or cell damage, such as during ischemia processes. This study aimed to identify DAMPs released during cold ischemia storage of human liver and analyze their ability to activate the inflammasome in myeloid cells and the possible implications in terms of short-term outcomes of liver transplantation. Methods 79 samples of organ preservation solution (OPS) from 79 deceased donors were collected after cold static storage. We used different analytical methods to measure DAMPs in these end-ischemic OPS (eiOPS) samples. We also used eiOPS in the human macrophage THP-1 cell line and primary monocyte cultures to study inflammasome activation. Findings Different DAMPs were identified in eiOPS, several of which induced both priming and activation of the NLRP3 inflammasome in human myeloid cells. Cold ischemia time and donation after circulatory death negatively influenced the DAMP signature. Moreover, the presence of oligomeric inflammasomes and interleukin-18 in eiOPS correlated with early allograft dysfunction in liver transplant patients. Interpretation DAMPs released during cold ischemia storage prime and activate the NLRP3 inflammasome in liver macrophages after transplantation, inducing a pro-inflammatory environment that will complicate the outcome of the graft. The use of pharmacological blockers targeting DAMPs or the NLRP3 inflammasome in liver ischemia during static cold storage or through extracorporeal organ support could be a suitable strategy to increase the success of liver transplantation.es
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dc.format.extent17es
dc.identifier.citationeBioMedicine. 2023 87:104419
dc.identifier.doihttps://doi.org/10.1016/j.ebiom.2022.104419
dc.identifier.urihttp://hdl.handle.net/10201/149294
dc.languageenges
dc.publisherElsevieres
dc.relationWe are particularly grateful for the generous contribution of the patients and the collaboration of Biobank Network of the Region of Murcia, BIOBANC-MUR, registered on the Registro Nacional de Biobancos with registration number B.0000859. BIOBANC-MUR is supported by the “Instituto de Salud Carlos III (proyecto PT20/00109)”, by “Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, IMIB” and by “Consejeria de Salud de la Comunidad Autónoma de la Región de Murcia. We would also like to thank Drs. Carlos Manuel Martínez-Cáceres and Jesús de la Peña for their helpful assistance in the immunohistochemical analyses. J.A.P. was funded by Instituto de Salud Carlos III (PI17/00489). A.B-M. was funded by Fundación Mutua Madrileña (AP171362019), Instituto de Salud Carlos III (PI20/00185) and Fundación Séneca (21655/PDC/ 21). P.P. was funded by grant PID2020-116709RB-I00 funded by MCIN/AEI/10.13039/501100011033, Fundación Séneca (grants 20859/PI/18, 21081/PDC/19 and 0003/COVI/20), Instituto de Salud Carlos III (grant DTS21/00080) and European Research Council (grant ERC-2019-PoC 899636). P.R. was funded by Instituto de Salud Carlos III (PI18/01302). F.L-R. has been co-financed by the European Social Fund (ESF) and the Youth European Initiative (YEI) under the Spanish Seneca Foundation (Spain) 21373/PDGI/20. SV.M. was funded by Instituto de Salud Carlos III (FI21/00073)es
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2352396422006016?via%3Dihub
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDAMPses
dc.subjectNLRP3
dc.subjectInflammasome
dc.subjectCold ischemia
dc.subjectDCD
dc.subjectDBD
dc.subjectLiver transplantation
dc.titleDanger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
relation.isAuthorOfPublication.latestForDiscovery547c4c2c-d906-4e1d-ae9a-0cdb40eef6d1
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