COLLAGENASE OF HEPATOCYTES AND SINUSOIDAL LIVER-CELLS IN THE REVERSIBILITY OF EXPERIMENTAL CIRRHOSIS OF THE LIVER

In order to explore the cellular source(s) and the behaviour of the collagenolytic activity previously described in rat liver homogenates, in the reversibility of experimental cirrhosis of the liver, enriched suspensions of hepatocytes and of sinusoidal liver cells were obtained by a procedure which employs low EDTA concentrations and no bacterial collagenase. Cell suspensions were prepared from three different groups of animals: 1) normal controls, 2) rats with CCl4-induced cirrhosis of the liver, and 3) rats with swine serum-induced cirrhosis of the liver. Animals were sacrificed in each group upon completion of treatment and also after 3, 6 and 12 months. In each liver wet weight and collagen concentration were determined, and collagenolytic activity of both enriched cell suspensions was measured separately. In addition, histological studies of liver tissue and ultrastructural examination of cell suspensions were performed by standard procedures. Enriched suspensions of both normal hepatocytes and sinusoidal liver cells display Ca2+-dependent collagenolytic activities. Both cell suspensions obtained from each of the two types of cirrhotic livers show normal or slightly increased average levels of collagenase activity at the time of treatment discontinuation, when average liver collagen content ranges from 6 to 10-fold over normal, suggesting that the normal collagenase/collagen ratio is disturbed and that collagenolytic activity is deeply decreased in relation to the actual liver collagen load. In addition, and despite wide individual variations, our data suggest that through a 12-month involution period of both types of experimental cirrhosis, there is an inversely proportional relation between liver collagen concentration and the collagenase/collagen ratio of both hepatocytes and sinusoidal liver cells, suggesting that the decrease in liver collagen is related to the increase in both collagenases. Morphologic and biochemical involution of fibrosis in both models of experimental liver cirrhosis was striking, although in the CCl4-treated group the parenchymal nodular pattern was still quite apparent at the end of the experiment. © 1990 Springer-Verlag.