Changes odf hapatic sinusoidal cell in fibrotic process of chronic liver disease-Three dimendional examination by confocal laser scanning microscopy-

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Sections (50-μm thick) obtained from normal and cirrhotic human livers were immunostained with anti-α smooth muscle actin (αSMA) antibody and were examined by confocal laser scanning microscopy, αSMA-positive stellate cells were distributed relatively evenly in the hepatic lobules of normal human livers and surrounded the sinusoids by the cytoplasmic processes showing three-dimensional (3-D) extension, On the other hand, αSMA-reactivity varied between regenerative nodules in cirrhotic livers. Stellate cells in the regenerative nodules showed reduction of αSMA-immunoreactivity of the cytoplasmic processes compared with that in normal livers and surrounded the sinusoids by cytoplasmic processes with two-dimensional extensions. In addition, αSMA-positive stellate cells were densely packed in fibrous septa and did not surround the lumens of the sinusoid by the cytoplasmic processes. These results showed that stellate cells have different characteristics compared with those in the normal liver.In rats, the sections from normal livers with and without ET-1 perfusion (1 or 400 nmol/l) were immunostained with anti-glial fibrillary acidic protein (GFAP) antibody. GFAP-positive stellate cells showed the entire views same as αSMA-positive stellate cells in the normal human liver and had the cytoplasmic processes with 3-D extensions. Furthermore, they tended to have longer cytoplasmic processes in the area between periportal and pericentral areas. Perfusion of ET-1 resulted in swelling of cell bodies with condensation of the intermediate filaments in GFAP-positive stellate cells compared with those perfused with buffer only However no apparent shortening of the cytoplasmic processes of the stellate cells was observed. From these results, it is suggested that stellate cells in the normal liver are not involved in the sinusoidal flow.