Sequential changes of extracellular matrix and proliferation of Ito cells with enhanced expression of desmin and actin in focal hepatic injury.

Immunohistochemical investigations were carried out on the properties of the cells and extracellular matrix (ECM) in focal hepatic injuries. A liquid nitrogen-cooled syringe needle was thrust into the rat liver. Necrotic areas became permeated with plasma within 24-hour period. Areas became strongly positive for fibronectin and were infiltrated with inflammatory cells positive for lysozyme. By the third day, Ito cells were proliferated in the peripheral portions of the damaged areas. These Ito cells showed enhanced immunostaining for desmin and actin but were negative for lysozyme. Interstitial fibers which were immunochemically positive for Types I and IV collagens, laminin, and fibronectin, began to increase from Day 3. They appeared on the rim of the hepatocytes adjacent to the damaged areas and extended into the injured regions with the Ito cells. An increase in basal laminas associated with capillaries and bile ducts also increased with a 1-day delay. The damaged areas were replaced by granulation tissue by Day 5. A rapid diminution then occurred in the granulation tissue, and normal hepatic tissue was restored in 7-10 days. These observations demonstrate that ECM changed in a sequential manner and then finally disappeared from the damaged site within 10 days. Although various cells, including parenchymal cells, macrophages, endothelial cells, and cholangiolar cells contributed to the healing of the damaged area, Ito cells, which exhibit unique phenotypic changes, presumably had a major role in the process.