Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver

David Sindram, Robert J. Porte, Maureane R. Hoffman, Rex C. Bentley, Pierre Alain Clavien

Research output: Contribution to journalArticleAcademicpeer-review

182 Citations (Scopus)

Abstract

Background and Aims:
Sinusoidal endothelial cell (SEC) apoptosis is a central feature of reperfusion injury in liver transplantation. Platelet sequestration occurs after transplantation with possible deleterious effects. We tested the hypothesis that platelets mediate SEC apoptosis.

Methods:
Livers were perfused after 24 hours of cold preservation in University of Wisconsin solution in an isolated perfused rat liver model. The perfusate contained isolated syngeneic red blood cells and purified platelets. Effects of inhibiting platelet adhesion on SEC apoptosis was tested using sialyl Lewis-X oligosaccharide (sLe(x)), a natural ligand of selectin adhesion molecules. Reperfusion injury was assessed by established markers of injury. Apoptosis was determined by TUNEL and electron microscopy.

Results:
A third of the circulating platelets was rapidly sequestered in the liver after reperfusion. This was associated with increased graft injury. Single platelets were adherent to sinusoidal lining without morphological or dynamic evidence of impairment of microcirculation. TUNEL staining revealed a 6-fold increase in the number of apoptotic SECs at 1 hour of reperfusion. No hepatocyte death or evidence of necrosis was detected up to 3 hours of reperfusion. Addition of sLe(x) inhibited adhesion and significantly reduced SEC apoptosis.

Conclusions:
Platelets cause SEC apoptosis upon reperfusion of liver grafts. Prevention of adhesion is protective. 

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalGastroenterology
Volume118
Issue number1
DOIs
Publication statusPublished - Jan 2000
Externally publishedYes

Bibliographical note

© 2000 by the American Gastroenterological Association

Fingerprint

Dive into the research topics of 'Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver'. Together they form a unique fingerprint.

Cite this