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Mediators of Inflammation
Volume 2010 (2010), Article ID 436145, 11 pages
http://dx.doi.org/10.1155/2010/436145
Research Article

Release of Danger Signals during Ischemic Storage of the Liver: A Potential Marker of Organ Damage?

1Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich Schiller University Jena, Drackendorfer Str.1, 07747 Jena, Germany
2The Centre for Molecular Medicine, Shaoxing People's Hospital, 312000 Shaoxing, China
3Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg and Essen, 45122 Essen, Germany
4Institute of Pathology, University Hospital Jena, 07747 Jena, Germany
5Department of Clinical Chemistry, Clinic of Endocrinology, University Hospital Essen, University of Duisburg and Essen, 45122 Essen, Germany

Received 7 July 2010; Accepted 4 October 2010

Academic Editor: F. D'Acquisto

Copyright © 2010 Anding Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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, HMGB1and MIF are more sensitive than liver enzymes to detect the additional mechanical damage inflicted on the organ graft during surgical manipulation.