Damage‐Associated Molecular Patterns Induce Inflammatory Injury During Machine Preservation of the Liver: Potential Targets to Enhance a Promising Technology

Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies have noted the presence of inflammatory molecules generated during MP. We hypothesized that there is a metabolism‐depen...

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Veröffentlicht in:Liver transplantation 2019-04, Vol.25 (4), p.610-626
Hauptverfasser: Scheuermann, Uwe, Zhu, Minghua, Song, Mingqing, Yerxa, John, Gao, Qimeng, Davis, Robert P., Zhang, Min, Parker, William, Hartwig, Matthew G., Kwun, Jean, Brennan, Todd V., Lee, Jaewoo, Barbas, Andrew S.
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Sprache:eng
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Zusammenfassung:Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies have noted the presence of inflammatory molecules generated during MP. We hypothesized that there is a metabolism‐dependent accumulation of damage‐associated molecular patterns (DAMPs) and inflammatory cytokines during MP and that these molecules provoke inflammation in the graft. To stratify groups by metabolic rate, MP was performed on rat livers from standard donors at 3 different temperatures: room temperature (RT), subnormothermic (30°C), and normothermic (37°C). Static cold storage at 4°C was included as a reference group. Following a 4‐hour preservation period, graft reperfusion was performed ex vivo at 37°C (n = 6 for all groups). Levels of DAMPs and inflammatory cytokines were measured, and their biological activity was assessed by determining toll‐like receptor (TLR) stimulation, inflammatory gene expression, and activation of cell death pathways. There was a time‐dependent increase in levels of DAMPs during MP with high‐mobility group box 1 and extracellular DNA levels increasing for all groups (P 
ISSN:1527-6465
1527-6473
DOI:10.1002/lt.25429