Reduced expression of the melanocortin-1 receptor in human liver during brain death.
OBJECTIVE
There is evidence that brain death has detrimental effects on peripheral organs. Clinical and experimental studies on organ donors showed marked inflammation in tissue samples of livers and kidneys collected during brain death. The inflammatory reaction is characterized by release of cytokines and inflammatory cell infiltration. Because melanocortins and their receptors are significant modulators of inflammation, we hypothesized that downregulation of melanocortin receptors during brain death could contribute to enhance inflammation.


METHODS
Using real-time polymerase chain reaction (PCR) analysis, we determined expression of melanocortin receptors in liver biopsies obtained from brain-dead organ donors before cold ischemia and in normal liver tissue during resection of benign focal lesions of the liver. Tissue biopsies were also analyzed for expression of intercellular adhesion molecule-1 (ICAM-1), which has a central function in inflammatory cell migration.


RESULTS
Expression of melanocortin-1 receptor (MC1R) mRNA was markedly reduced in liver samples obtained from brain-dead organ donors compared to hepatic tissue collected during resection of benign focal lesions of the liver. Conversely, expression of the adhesion molecule ICAM-1 was significantly increased in livers of brain-dead organ donors.


CONCLUSIONS
Disruption of the endogenous anti-inflammatory circuit based on MC1R could contribute to tissue damage during brain death.
Gatti
Stefano
S
Liver Transplantation Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy.
Colombo
Gualtiero
G
Turcatti
Flavia
F
Lonati
Caterina
C
Sordi
Andrea
A
Bonino
Ferruccio
F
Lipton
James M
JM
Catania
Anna
A
D000328:Adult; D000368:Aged; D001706:Biopsy; D001926:Brain Death / Q000276:immunology* / Q000503:physiopathology*; D002448:Cell Adhesion / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006505:Hepatitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D015854:Up-Regulation / Q000276:immunology; D000521:alpha-MSH / Q000276:immunology* / Q000378:metabolism
D012333:RNA, Messenger; D044102:Receptor, Melanocortin, Type 1; D018799:Intercellular Adhesion Molecule-1; D000521:alpha-MSH