Factor VIII expression by sinusoidal endothelial cells in fibrosis-non-associated hepatic necrosis

We previously reported that sinusoidal capillarization and arterialization proceed with the advance of the stages of hepatocarcinogenesis in rats. To elucidate the inducing role of arterial blood flow in the development of si nusoidal capillarization, we used the portal ligated liver that absolutely received arterial blood and investigated phenotypic and morphological chang es of sinu-soidal endothelial cells. At various time intervals after ligati on of portal branch, the liver was perfusion-fixed and examined by immunohi stochemistry and electron microscopy. In untreated livers, factor VIII-rela ted antigen (F-VIII) was not expressed in the liver lobule. By portal ligat ion, massive hepatic necrosis occurred, but normal structure was restored i n a week. At 3 weeks after ligation, F-VIII was expressed along the sinusoi ds in the midseptal zone, increased in positive area at 5 weeks, and prevai led in the liver lobule at 14 weeks. Electron microscopically, at 14 weeks, sinusoidal endothelial fenestrae remained intact, although decreased in nu mber, being associated with incomplete basement membrane. The present resul ts indicate that arterialization induces the phenotypic change but not enti rely the morphological change of sinusoidal endothelial cells into capillar y ones in the non-neoplastic liver tissues.