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Targeting Circulating Leukocytes and Pyroptosis During Ex Vivo Lung Perfusion Improves Lung Preservation

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dc.contributor.authorNoda, K-
dc.contributor.authorTane, S-
dc.contributor.authorHaam, SJ-
dc.contributor.authorD'Cunha, J-
dc.contributor.authorHayanga, AJ-
dc.contributor.authorLuketich, JD-
dc.contributor.authorShigemura, N-
dc.date.accessioned2018-10-04T06:13:53Z-
dc.date.available2018-10-04T06:13:53Z-
dc.date.issued2017-
dc.identifier.issn0041-1337-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/16386-
dc.description.abstractBACKGROUND: The role of the circulating leukocytes in lungs and their relationship with circulating proinflammatory cytokines during ischemia-reperfusion injury is not well understood. Using ex vivo lung perfusion (EVLP) to investigate the pathophysiology of isolated lungs, we aimed to identify a therapeutic target to optimize lung preservation leading to successful lung transplantation.
METHODS: Rat heart-lung blocks were placed on EVLP for 4 hours with or without a leukocyte-depleting filter (LF). After EVLP, lung grafts were transplanted, and posttransplant outcomes were compared.
RESULTS: Lung function was significantly better in lung grafts on EVLP with a LF than in lungs on EVLP without a LF. The interleukin (IL)-6 levels in the lung grafts and EVLP perfusate were also significantly lower after EVLP with a LF. Interestingly, IL-6 levels in the perfusate did not increase after the lungs were removed from the EVLP circuit, indicating that the cells trapped by the LF were not secreting IL-6. The trapped cells were analyzed with flow cytometry to detect apoptosis and pyroptosis: 26% were pyroptotic (Caspase-1-positive). After transplantation, there was better graft function and less inflammatory response if a LF was used or a caspase-1 inhibitor was administered during EVLP.
CONCLUSIONS: Our data demonstrated that circulating leukocytes derived from donor lungs, and not circulating proinflammatory cytokines substantially impaired the quality of lung grafts through caspase-1-induced pyroptotic cell death during EVLP. Removing these cells with a LF and/or inhibiting pyroptosis of the cells can be a new therapeutic approach leading to long-term success after lung transplantation.
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dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHCardiopulmonary Bypass-
dc.subject.MESHCaspase 1-
dc.subject.MESHCytokines-
dc.subject.MESHHumans-
dc.subject.MESHInflammation-
dc.subject.MESHInterleukin-6-
dc.subject.MESHLeukocytes-
dc.subject.MESHLung-
dc.subject.MESHLung Transplantation-
dc.subject.MESHMale-
dc.subject.MESHMicrocirculation-
dc.subject.MESHOrgan Preservation-
dc.subject.MESHPerfusion-
dc.subject.MESHPyroptosis-
dc.subject.MESHRats-
dc.subject.MESHRats, Inbred Lew-
dc.subject.MESHRespiratory Function Tests-
dc.subject.MESHTreatment Outcome-
dc.titleTargeting Circulating Leukocytes and Pyroptosis During Ex Vivo Lung Perfusion Improves Lung Preservation-
dc.typeArticle-
dc.identifier.pmid28452921-
dc.contributor.affiliatedAuthor함, 석진-
dc.type.localJournal Papers-
dc.identifier.doi10.1097/TP.0000000000001798-
dc.citation.titleTransplantation-
dc.citation.volume101-
dc.citation.number12-
dc.citation.date2017-
dc.citation.startPage2841-
dc.citation.endPage2849-
dc.identifier.bibliographicCitationTransplantation, 101(12). : 2841-2849, 2017-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1534-6080-
dc.relation.journalidJ000411337-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Thoracic & Cardiovascular Surgery
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