Granuloma formation in the liver of Balb/c mice intoxicated with carbon tetrachloride.

Hepatic granulomas induced by a single or several subcutaneous injections of carbon tetrachloride (CCl4) in Balb/c mice were examined electronmicroscopically and immunocytochemically. Stellate cells (fat-storing cells; lipocytes; Ito cells) were identified by the detection of cytoplasmic desmin, while T-lymphocytes and monocytes/macrophages were identified with monoclonal antibodies Thy 1.2 and MOMA-2, respectively. Following pericentral necrosis induced with CCl4, clear foci containing lymphocytes, monocytes, macrophages and perisinusoidal stellate cells occurred in the surrounding hepatic parenchyma on day 5. These clear foci developed to granulomas with increasing numbers of macrophages and stellate cells. Mitotic and apoptotic figures in randomly distributed macrophages, and direct contacts between macrophages and stellate cells were frequently seen within the granulomas. The stellate cells were characterized by a well-developed granular endoplasmic reticulum and Golgi complex. Collagen fibrils were closely applied to the stellate cells and connective tissue septa extended between neighboring granulomas and/or the pericentral necrotic areas after several injections of CCl4. CCl4-induced hepatic granulomas provide a model for investigating paracrine and/or autocrine modulation within a well-organized microenvironment during progressive hepatic inflammation and fibrosis.