A. Sugihara et al., Evaluation of role of mast cells in the development of liver fibrosis using mast cell-deficient rats and mice, J HEPATOL, 30(5), 1999, pp. 859-867
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 whethe
r mast cells are involved in the development of liver fibrosis.
Methods: Liver fibrosis was induced in rats by bile duct resection (BDR), a
nd by intraperitoneal injections of carbon tetrachloride (CCl4) or porcine
serum, and in mice by intragastric administrations of CCl4, and BDR. The de
gree 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 fou
nd principally in portal areas, and their average density was 200-300/cm(2)
liver section. BDR, and treatments with CCl4 and porcine serum increased t
he 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 hig
her level than that in +/+ rats. However, the average densities of mast cel
ls 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 the
ir density, whereas these treatments induced liver fibrosis and markedly in
creased 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 (aver
age, less than 1), and was not increased by treatment with CCl4.
Conclusions: The present results indicate that mast cells play no role in t
he development of liver fibrosis in rats and mice.