Tissue distribution, quantitation and proliferation kinetics of fat-storing cells in carbon tetrachloride-injured rat liver

Abstract

In this study, we have investigated the cell population kinetics of fat-storing cells in livers of rats intoxicated with CCl 4. Fat-storing cells were identified in cryostat sections by immunoperoxidase staining of desmin. The peroxidase label was visualized using diaminobenzidine/hydrogen peroxide containing Ni 2+ and Co 2+-ions (Nico/diaminobenzidine method). In normal rats, we found 12.8 fat-storing cells/0.1 mm 2 in periportal areas vs. 9.4 in pericentral fields. After one injection of CCl 4, the number of pericentral cells increased gradually to reach a maximum of 39.4 cells/0.1 mm 2 96 hr after injection. The desmin staining intensity of the pericentral fat-storing cells increased from 48 hr onward. At 72 to 120 hr, strongly stained cells were observed in pericentral areas and in bands of tissue between adjacent central veins, reminiscent of the connective tissue septa in fibrotic livers. In the periportal areas the number of fat-storing cells was not altered. After a second and third injection of CCl 4, the number of cells increased further in the pericentral areas. When more than three injections were given, the pericentral fat-storing cell population reached a new steady state with the cell number being seven times higher than in control animals. Proliferation of fat-storing cells at different stages of CCl 4 intoxication was studied by intravenous administration of 3 H-thymidine, followed by combined desmin staining and autoradiography. Autoradiographical labeling of fat-storing cells was nearly absent in control animals and at 24 hr after a single CCl 4 injection. At 48 to 96 hr, labeling indices of pericentral fat-storing cells were significantly higher than in control animals, with a maximum at 72 hr when 22.9% of the cells were labeled. After multiple injections of CCl 4, labeling indices between 4.9% and 8.4% were found. We conclude that fibrogenesis is preceded by a strong expansion of the fat-storing cell population in the pericentral areas of the liver lobules and in bands of tissue between adjacent central veins. Local proliferation is an important mechanism underlying the expansion of this cell population. (Hepatology 1991;13:1193-1202.)