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Ex Vivo Lung Perfusion Improves the Inflammatory Signaling Profile of the Porcine Donor Lung Following Transplantation

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Titel: Ex Vivo Lung Perfusion Improves the Inflammatory Signaling Profile of the Porcine Donor Lung Following Transplantation
Autoren: Stone, John P, Ball, Alexandra L, Crichley, William, Yonan, Nizar, Liao, Quiming, Sjöberg, Trygve, Steen, Stig, Fildes, James E
Quelle: Stone, J P, Ball, A L, Crichley, W, Yonan, N, Liao, Q, Sjöberg, T, Steen, S & Fildes, J E 2020, 'Ex Vivo Lung Perfusion Improves the Inflammatory Signaling Profile of the Porcine Donor Lung Following Transplantation', Transplantation, vol. 104, no. 9, pp. 1899-1905. https://doi.org/10.1097/TP.0000000000003338
Verlagsinformationen: Ovid Technologies (Wolters Kluwer Health), 2020.
Publikationsjahr: 2020
Schlagwörter: Male, 0301 basic medicine, Proteome, Swine, Lung/metabolism, DNA, Mitochondrial, Lung Transplantation/methods, DNA, Mitochondrial/blood, 03 medical and health sciences, Perfusion/methods, Animals, Lung, Inflammation, 0303 health sciences, Signal Transduction/physiology, Inflammation/prevention & control, Organ Preservation/methods, DNA, Organ Preservation, Tissue Donors, 3. Good health, Perfusion, Mitochondrial/blood, Female, Lung Transplantation, Signal Transduction
Beschreibung: Background. Primary graft dysfunction and allograft rejection represent major caveats to successful lung transplantation. Reducing inflammation in donor lungs before transplantation may improve outcomes. Evidence exists that ex vivo lung perfusion (EVLP) can alter the donor lung environment, although the mechanisms remain unclear. This study aimed to characterize the inflammatory signaling profile of the lung following standard and EVLP transplant and delineate the immediate impact on the recipient circulation. Methods. Female recipient pigs (n = 12) were randomized to undergo left lung transplantation from male donors either using the gold standard protocol (static cold storage) or following 3 hours of EVLP. The relative phosphorylation of 44 phosphokinases and the relative expression of 35 apoptosis-related molecules were profiled within the donor lung 24 hours posttransplantation. Results. A global profile of mitochondrial salvage and cell survival was observed in the EVLP lung tissue compared with lungs undergoing standard transplantation. This included increased phosphorylation of downstream prosignaling kinases, including ERK1/2 and FAK. In addition, there was upregulated expression of the antiapoptotic proteins Bcl-2, HSP-70, LIVIN, and PON2 with downregulation of apoptosis inducing mitochondrial associated molecules, including clusterin, cytochrome C, and HTRA2/OMI. In the early postoperative period, there were significantly lower levels of circulating mitochondrial DNA in recipients receiving EVLP lungs compared with a standard transplant (P = 0.016). Genomic DNA did not differ between groups, with donor DNA undetectable at all time points. Conclusions. EVLP alters the inflammatory signaling profile of the donor lung before transplantation, with a global cell survival and antiapoptotic signature.
Publikationsart: Article
Sprache: English
ISSN: 0041-1337
DOI: 10.1097/tp.0000000000003338
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/32502131
https://research.manchester.ac.uk/en/publications/49922403-f248-46a2-8148-84f7c481a7de
https://doi.org/10.1097/TP.0000000000003338
https://www.research.manchester.ac.uk/portal/en/publications/ex-vivo-lung-perfusion-improves-the-inflammatory-signaling-profile-of-the-porcine-donor-lung-following-transplantation(49922403-f248-46a2-8148-84f7c481a7de).html
https://lup.lub.lu.se/record/7240555f-69ff-4646-89e9-e7b61bf11f00
https://portal.research.lu.se/portal/en/publications/ex-vivo-lung-perfusion-improves-the-inflammatory-signaling-profile-of-the-porcine-donor-lung-following-transplantation(7240555f-69ff-4646-89e9-e7b61bf11f00).html
https://www.ncbi.nlm.nih.gov/pubmed/32502131
https://pubmed.ncbi.nlm.nih.gov/32502131/
https://journals.lww.com/10.1097/TP.0000000000003338
Dokumentencode: edsair.doi.dedup.....7ab9b2d2bef1f5a9a7ed3d1e88ceb1a3
Datenbank: OpenAIRE
Beschreibung
Abstract:Background. Primary graft dysfunction and allograft rejection represent major caveats to successful lung transplantation. Reducing inflammation in donor lungs before transplantation may improve outcomes. Evidence exists that ex vivo lung perfusion (EVLP) can alter the donor lung environment, although the mechanisms remain unclear. This study aimed to characterize the inflammatory signaling profile of the lung following standard and EVLP transplant and delineate the immediate impact on the recipient circulation. Methods. Female recipient pigs (n = 12) were randomized to undergo left lung transplantation from male donors either using the gold standard protocol (static cold storage) or following 3 hours of EVLP. The relative phosphorylation of 44 phosphokinases and the relative expression of 35 apoptosis-related molecules were profiled within the donor lung 24 hours posttransplantation. Results. A global profile of mitochondrial salvage and cell survival was observed in the EVLP lung tissue compared with lungs undergoing standard transplantation. This included increased phosphorylation of downstream prosignaling kinases, including ERK1/2 and FAK. In addition, there was upregulated expression of the antiapoptotic proteins Bcl-2, HSP-70, LIVIN, and PON2 with downregulation of apoptosis inducing mitochondrial associated molecules, including clusterin, cytochrome C, and HTRA2/OMI. In the early postoperative period, there were significantly lower levels of circulating mitochondrial DNA in recipients receiving EVLP lungs compared with a standard transplant (P = 0.016). Genomic DNA did not differ between groups, with donor DNA undetectable at all time points. Conclusions. EVLP alters the inflammatory signaling profile of the donor lung before transplantation, with a global cell survival and antiapoptotic signature.
ISSN:00411337
DOI:10.1097/tp.0000000000003338