Immunohistochemical and ultrastructural study of hepatic sinusoidal linings during dichloropropanol-induced acute hepatic necrosis.

An acute phase of severe hepatic necrosis induced by dichloropropanol was examined immunohistochemically and ultrastructurally, in order to study chronological changes of sinusoidal morphology during acute hepatic injury. Male Wistar rats were injected with 1,3-dichloro-2-propanol (DC2P) and sacrificed at various intervals after the injections. DC2P-injected rats showed zonal necrosis of the centrilobular space with a peak from 24 to 48 h after the injection. Destruction of sinusoidal linings appeared at 4 h, and was gradually aggravated along the advancing hepatocytic necrosis. Monocytic influx into the necrotic areas was initiated at 6 h. At 48 h, collapsed centrilobular spaces showed a loss of most sinusoidal structures with active phagocytosis of macrophages, proliferation of perisinusoidal cells, and accumulation of collagen fibrils. At 72 h, there were many regenerating sinusoidal structures, which were composed of rather thick and less fenestrated endothelium and underlying multilayered processes of mesenchymal cells, along the regenerating hepatocytes. In these areas, occasional junctions between regenerating hepatocytes and mesenchymal cells were seen. Reconstruction of sinusoidal linings was closely related to the hepatocytic regeneration, and a hepatocytic-mesenchymal interaction might participate in this morphodynamic course of the sinusoidal reconstruction.