IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL ANALYSES OF IN-SITU ACTIVATION OF HEPATIC STELLATE CELLS AROUND PROPIONIBACTERIUM ACNES-INDUCED GRANULOMAS IN THE RAT-LIVER

Stellate cells embrace the hepatic sinusoids as pericytes. To demonstr ate their activation in juxta-sinusoidal location, we induced hepatic granulomatous inflammation, which did not accompany liver injury nor f ibrosis, by administrating a low dose (10 mg/kg b.w.) of heat-killed P ropionibacterium ames into rats. Macrophages and lymphocytes migrated out of the sinusoid and made compact granulomas in the space of Disse. Stellate cells which faced on the granulomas were closely attached to the sinusoidal endothelial cells and extended projections into the sp aces between the constituent mononuclear cells of granulomas. They did not migrate into granulomas nor displayed mitosis. Immunohistochemica lly, stellate cells around the granulomas expressed alpha-smooth muscl e actin (alpha-SMA), whereas those in the non-granulomatous regions di d not. Small deposits of type III collagen were found at the periphery of granulomas. Biochemical analysis showed an increased amount of alp ha-SMA protein and type III collagen mRNA in the granuloma-bearing liv er. Transforming growth factor-beta and platelet-derived growth factor were detected within the granulomas. The present study has revealed t hat stellate cells are activated in situ by extrasinusoidal macrophage s in a paracrine manner without being detached from the sinusoidal wal l.