Pro-inflammatory agents accumulate during donor liver cold preservation: a study on increased adhesion molecule expression and abrogation by curcumin in cultured endothelial cells.
Cold hypoxia and re-oxygenation during organ preservation leads to a variety of stresses, including expression of adhesion molecules, which can promote inflammatory responses and compromised function. These studies were undertaken to investigate the pro-inflammatory activities of factors present in the vascular bed at the end of cold storage in livers during clinical hepatic transplantation. Effluent perfusate (termed pro-inflammatory vascular effluent-PVE) washed out at the end of cold storage, was collected from 10 donor livers, and used in a bio-assay with cultured endothelial cells exposed to cold hypoxia and re-oxygenation. Adhesion molecule expressions for intercellular adhesion molecule 1 (ICAM-1) and E-selectin were measured using molecular techniques and Northern blot analyses. Cells exposed to PVE during warming showed up-regulation of both ICAM-1 and E-selectin (p<0.05 in both cases) in all 10 preparations. Addition of curcumin (an inhibitor of nuclear transcription for the inflammatory cascade) abrogated expression of adhesion molecules at a statistically significant level for ICAM-1 in 8/10 PVE, and for E-selectin in all 10 PVE. We conclude that pro-inflammatory agents accumulate in livers during clinical liver transplantation and on rewarming may add to graft injury.
Fuller
Barry
B
University Department of Surgery and Liver Transplant Unit, Royal Free and University College Medical School, London NW3 2QG, UK. b.fuller@rfc.ucl.ac.uk
Dijk
Sas
S
Butler
Patrice
P
Hoang
Van
V
Davidson
Brian
B
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D015925:Cryopreservation; D003474:Curcumin / Q000494:pharmacology; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D014019:Tissue Donors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1; D003474:Curcumin