title: Release of danger signals during ischemic storage of the liver: a potential marker of organ damage?
abstract: Liver grafts suffer from unavoidable injury due to ischemia and manipulation before implantation. Danger signals such as high-mobility group box -1(HMGB1) and macrophage migration inhibitory factor (MIF) play a pivotal role in the immune response. We characterized the kinetics of their release into the effluent during cold/warm ischemia and additional manipulation-induced mechanical damage. Furthermore, we evaluated the relationship between HMGB1/MIF release and ischemic/mechanical damage. Liver enzymes and protein in the effluent increased with increasing ischemia time. HMGB1/MIF- release correlated with the extent of hepatocellular injury. With increasing ischemia time and damage, HMGB1 was translocated from the nucleus to the cytoplasma as indicated by weak nuclear and strong cytoplasmic staining. Enhancement of liver injury by mechanical damage was indicated by an earlier HMGB1 translocation into the cytoplasm and earlier release of danger signals into the effluent. Our results suggest that determination of HMGB1 and MIF reflects the extent of ischemic injury. Furthermore, HMGB1 and MIF are more sensitive than liver enzymes to detect the additional mechanical damage inflicted on the organ graft during surgical manipulation.
authors.affiliation: Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich Schiller University Jena, Drackendorfer Str.1, 07747 Jena, Germany.
authors.forename: Anding
authors.initials: A
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Jin
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
authors.forename: Meihong
authors.initials: M
authors.lastname: Deng
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Martina
authors.initials: M
authors.lastname: Bröcker-Preuss
authors.forename: Uta
authors.initials: U
authors.lastname: Dahmen
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D050377:Cold Ischemia; D024243:HMGB1 Protein / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply* / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008297:Male; D009926:Organ Preservation / Q000009:adverse effects; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013314:Stress, Mechanical; D052096:Warm Ischemia
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat