Morphological and functional alterations to sinusoidal endothelial cells in the early phase of endotoxin-induced liver failure after partial hepatectomy in rats

Liver failure following major hepatectomy is characterized pathologically by massive hepatic necrosis, which is thought to begin with injury of sinusoidal endothelial cells (SECs). To examine the early events of SECs leading to hepatic damage, we performed time-course analyses of the morphological and functional perturbation of SECs after endotoxin administration to hepatectomized rats. At 1.5 h after endotoxin injection, when hepatocellular damage was not yet evident, SECs showed augmented expression of intercellular adhesion molecule-1, with frequent adherence of infiltrating leucocytes and ultrastructural features of defenestration and hypertrophied cytoplasm enriched with cell organelles. The serum level of hyaluronate, as an indicator of the functional state of SECs, was significantly elevated. At 3 h, SECs underwent necrosis and disruption, accompanied by fibrin deposits with concomitant hepatocellular necrosis. The morphological and functional alterations of SECs precede necrotic changes in hepatocytes and SECs in endotoxin-induced liver failure after partial hepatectomy.