Endogenous protease inhibitor uptake within the graft during reperfusion in human liver transplantation.
J Hepatobiliary Pancreat Sci
; 17(2): 158-65, 2010 Mar.
Article
em En
| MEDLINE
| ID: mdl-19452123
ABSTRACT
BACKGROUND:
In experimental liver transplantation, endogenous protease inhibitors alleviate ischemia-reperfusion (I/R) injury by inhibiting proteolysis and by direct anti-inflammatory actions. We described the kinetics of endogenous protease inhibitors and explored their anti-inflammatory potential during reperfusion and their effects on graft function in human liver transplantation.METHODS:
We measured circulating levels of protease inhibitors (secretory leukocyte proteinase inhibitor, SLPI; tissue inhibitor of metalloproteinases-1, TIMP-1) and proteolytic enzymes (elastase; matrix metalloproteinase-9, MMP-9) with ELISA, and neutrophil and monocyte CD11b and L-selectin expression with flow cytometry during liver transplantation in ten patients. To assess changes within the graft during reperfusion, blood samples from portal and hepatic veins were obtained simultaneously.RESULTS:
Circulating SLPI and TIMP-1 levels decreased during surgery. During initial reperfusion, the transhepatic SLPI gradient was -27 (-35 to -22) ng/ml, P = 0.005, and TIMP-1 -510 (-636 to -362) ng/ml, P = 0.005, indicating graft protease inhibitor uptake. Concomitantly, hepatic phagocyte activation and sequestration as well as elastase and MMP-9 release into the circulation occurred. The transhepatic SLPI gradient correlated with postoperative liver enzymes (ALT R = -0.648, P = 0.043; ALP R = -0.661, P = 0.038; bilirubin R = -0.821, P = 0.004; GGT R = -0.648, P = 0.043).CONCLUSIONS:
The results suggest a relative shortage of protease inhibitors within the liver during reperfusion, which may contribute to the development of graft injury.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Traumatismo por Reperfusão
/
Rejeição de Enxerto
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article