Evaluation of role of mast cells in the development of liver fibrosis using mast cell-deficient rats and mice

Background/Aims: Several studies have suggested that mast cells participate in the development of liver fibrosis in rodent models. In this study mast cell-deficient mutant Ws/Ws rats and W/W-v mice were used to examine whether mast cells are involved in the development of liver fibrosis. Methods: Liver fibrosis was induced in rats by bile duct resection (BDR), and by intraperitoneal injections of carbon tetrachloride (CCl4) or porcine serum, and in mice by intragastric administrations of CCl4, and BDR. The degree of fibrosis was evaluated by measuring the hydroxyproline content (mu g/mg tissue) of the liver as an index of the collagen content. The density of mast cells (number/cm(2) liver section) was determined by counting mast cells in liver sections stained with alcian blue. Results: In the liver of control non-mutant (+/+) rats, mast cells were found principally in portal areas, and their average density was 200-300/cm(2) liver section. BDR, and treatments with CCl4 and porcine serum increased the density of mast cells in the liver of +/+ rats several-fold, and induced liver fibrosis, increasing the liver hydroxyproline content markedly. BDR, and treatments with CCl4 and porcine serum also induced liver fibrosis in Ws/Ws rats, increasing the liver hydroxyproline content to a similar or higher level than that in +/+ rats. However, the average densities of mast cells in the liver of Ws/Ws rats after BDR and treatment with CCl4 and porcine serum were at most 10.2/cm(2) liver section. The density of mast cells in the liver of control +/+ mice was extremely low (average, less than 2), and neither BDR nor treatment with CCl4 caused any significant increase in their density, whereas these treatments induced liver fibrosis and markedly increased the liver hydroxyproline content. Furthermore, treatment with CCl4 induced fibrosis in the liver of W/W-v mice similarly to that in +/+ mice, but the density of mast cells in the liver of W/W-v mice was very low (average, less than 1), and was not increased by treatment with CCl4. Conclusions: The present results indicate that mast cells play no role in the development of liver fibrosis in rats and mice.