Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver.
OBJECTIVE
To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury.


METHODS
The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution.


RESULTS
In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 min of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kappaB was found between control and P-selectin antibody-treated livers.


CONCLUSIONS
In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.
Wyllie
Samuel
S
Department of Surgery, Liver Transplant Center Laboratory, Baylor College of Medicine, Houston, TX 77030, USA. swyllie@bcm.tmc.edu
Barshes
Neal R
NR
Gao
Feng Qin
FQ
Karpen
Saul J
SJ
Goss
John A
JA
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D000906:Antibodies; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D050377:Cold Ischemia; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D009504:Neutrophils / Q000276:immunology; D019188:Organ Preservation Solutions; D019007:P-Selectin / Q000235:genetics / Q000276:immunology*; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism; D011887:Raffinose; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013997:Time Factors
D000906:Antibodies; D007328:Insulin; D016328:NF-kappa B; D019188:Organ Preservation Solutions; D019007:P-Selectin; D012333:RNA, Messenger; C055206:University of Wisconsin-lactobionate solution; D018799:Intercellular Adhesion Molecule-1; D000493:Allopurinol; D001219:Aspartate Aminotransferases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D019803:Glutathione Disulfide