Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in context
Summary: Background: 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 li...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422006016 |
| _version_ | 1828089800031207424 |
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| author | Fernando Lucas-Ruiz Sandra V. Mateo Marta Jover-Aguilar Felipe Alconchel Laura Martínez-Alarcón Carlos de Torre-Minguela Daniel Vidal-Correoso Francisco Villalba-López Víctor López-López Antonio Ríos-Zambudio José A. Pons Pablo Ramírez Pablo Pelegrín Alberto Baroja-Mazo |
| author_facet | Fernando Lucas-Ruiz Sandra V. Mateo Marta Jover-Aguilar Felipe Alconchel Laura Martínez-Alarcón Carlos de Torre-Minguela Daniel Vidal-Correoso Francisco Villalba-López Víctor López-López Antonio Ríos-Zambudio José A. Pons Pablo Ramírez Pablo Pelegrín Alberto Baroja-Mazo |
| author_sort | Fernando Lucas-Ruiz |
| collection | DOAJ |
| description | Summary: Background: 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. Funding: Fundación Mutua Madrileña and Instituto de Salud Carlos III, Madrid, Spain. |
| first_indexed | 2024-04-11T05:47:31Z |
| format | Article |
| id | doaj.art-2c28ea19bada4e2e8e37f7e5119246df |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-11T05:47:31Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-2c28ea19bada4e2e8e37f7e5119246df2022-12-22T04:42:09ZengElsevierEBioMedicine2352-39642023-01-0187104419Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in contextFernando Lucas-Ruiz0Sandra V. Mateo1Marta Jover-Aguilar2Felipe Alconchel3Laura Martínez-Alarcón4Carlos de Torre-Minguela5Daniel Vidal-Correoso6Francisco Villalba-López7Víctor López-López8Antonio Ríos-Zambudio9José A. Pons10Pablo Ramírez11Pablo Pelegrín12Alberto Baroja-Mazo13Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, SpainMolecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, SpainTransplant Unit, Surgery Service, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain; Biomedical Research Institute of Murcia IMIB-Pascual Parrilla, Murcia, SpainTransplant Unit, Surgery Service, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain; Biomedical Research Institute of Murcia IMIB-Pascual Parrilla, Murcia, SpainTransplant Unit, Surgery Service, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain; Biomedical Research Institute of Murcia IMIB-Pascual Parrilla, Murcia, SpainMolecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, SpainMolecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, SpainMolecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, SpainTransplant Unit, Surgery Service, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain; Biomedical Research Institute of Murcia IMIB-Pascual Parrilla, Murcia, SpainTransplant Unit, Surgery Service, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain; Biomedical Research Institute of Murcia IMIB-Pascual Parrilla, Murcia, SpainLiver Transplantation Unit, Gastroenterology and Hepatology Service, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, SpainTransplant Unit, Surgery Service, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain; Biomedical Research Institute of Murcia IMIB-Pascual Parrilla, Murcia, SpainMolecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, Spain; Department of Biochemistry and Molecular Biology B and Immunology, Faculty of Medicine, University of Murcia, 30120, Murcia, Spain; Corresponding author. Campus de Ciencias de la Salud, Edificio LAIB, Office 4.15, Ctra. Buenavista s/n, 30120, Murcia, Spain.Molecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120, Murcia, Spain; Corresponding author. Campus de Ciencias de la Salud, Edificio LAIB, Office 4.21, Ctra. Buenavista s/n, 30120, Murcia, Spain.Summary: Background: 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. Funding: Fundación Mutua Madrileña and Instituto de Salud Carlos III, Madrid, Spain.http://www.sciencedirect.com/science/article/pii/S2352396422006016DAMPsNLRP3InflammasomeCold ischemiaDCDDBD |
| spellingShingle | Fernando Lucas-Ruiz Sandra V. Mateo Marta Jover-Aguilar Felipe Alconchel Laura Martínez-Alarcón Carlos de Torre-Minguela Daniel Vidal-Correoso Francisco Villalba-López Víctor López-López Antonio Ríos-Zambudio José A. Pons Pablo Ramírez Pablo Pelegrín Alberto Baroja-Mazo Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in context EBioMedicine DAMPs NLRP3 Inflammasome Cold ischemia DCD DBD |
| title | Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in context |
| title_full | Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in context |
| title_fullStr | Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in context |
| title_full_unstemmed | Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in context |
| title_short | Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantationResearch in context |
| title_sort | danger signals released during cold ischemia storage activate nlrp3 inflammasome in myeloid cells and influence early allograft function in liver transplantationresearch in context |
| topic | DAMPs NLRP3 Inflammasome Cold ischemia DCD DBD |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422006016 |
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