The Distinct Innate Immune Response of Warm Ischemic Injured Livers during Continuous Normothermic Machine Perfusion

• Published in: International journal of molecular sciences 2023-08, Vol.24 (16), p.12831
• Main Authors: Blondeel, Joris, Gilbo, Nicholas, Heedfeld, Veerle, Wylin, Tine, Libbrecht, Louis, Jochmans, Ina, Pirenne, Jacques, Korf, Hannelie, Monbaliu, Diethard
• Format: Article
• Language: English
• Subjects: animal experiment; animal model; animal tissue; antibiotic agent; Apoptosis; aspartate aminotransferase; bicarbonate; cell function; cell motion; Chirurgie; Comparative analysis; controlled study; cytokine; cytokine release; Cytokines; Endoplasmic reticulum; endoplasmic reticulum stress; gelatin succinate; gluconate calcium; hemoperfusion; heparin; histopathology; Human health sciences; hypertransaminasemia; Immune response; Immunity, Innate; immunohistochemistry; inflammation; innate immunity; insulin; interleukin 10; interleukin 8; Ischemia; ischemia-reperfusion injury; lactic acid; Leukocytes; Liver; liver cell damage; liver graft; liver ischemia; liver perfusion; liver transplantation; Liver transplants; male; messenger RNA; mRNA expression level; neutrophil; nonhuman; normothermic machine perfusion; Perfusion; phenotype; porcine model; preservation; protein expression level; Proteins; Reperfusion; reperfusion injury; Sciences de la santé humaine; Scientific equipment and supplies industry; signal transduction; Surgery; taurocholic acid; transforming growth factor beta; Transforming growth factors; Transplantation; Transplants & implants; Tumor necrosis factor; Tumor necrosis factor-TNF; vasodilator agent
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241612831

Although normothermic machine perfusion (NMP) provides superior preservation of liver grafts compared to static cold storage and allows for viability testing of high-risk grafts, its effect on the liver immune compartment remains unclear. We investigated the innate immune response during 6 h of continuous NMP (cNMP) of livers that were directly procured (DP, n = 5) or procured after 60 min warm ischemia (WI, n = 5), followed by 12 h of whole blood (WB) reperfusion. WI livers showed elevated transaminase levels during cNMP but not after WB reperfusion. Perfusate concentrations of TNF-α were lower in WI livers during cNMP and WB reperfusion, whereas IL-8 concentrations did not differ significantly. TGF-β concentrations were higher in WI livers during NMP but not after WB reperfusion, whereas IL-10 concentrations were similar. Endoplasmic stress and apoptotic signaling were increased in WI livers during cNMP but not after WB reperfusion. Additionally, neutrophil mobilization increased to a significantly lesser extent in WI livers at the end of NMP. In conclusion, WI livers exhibit a distinct innate immune response during cNMP compared to DP livers. The cytokine profile shifted towards an anti-inflammatory phenotype during cNMP and WB reperfusion, and pro-apoptotic signaling was stronger during cNMP. During WB reperfusion, livers exhibited a blunted cytokine release, regardless of ischemic damage, supporting the potential reconditioning effect of cNMP.