Involvement of mast cells in acute hepatic injury induced by galactosamine and lipopolysaccharide in mice

We investigated the possible involvement of mast cells in acute hepatic injury induced by galactosamine (GalN, 20 mg/mouse) and lipopolysaccharide (LPS, 15 ng/mouse) (GalN/LPS) in mice. Histidine decarboxylase (HDC) mRNA expression in the liver as well as serum ALT level was increased with time after GalN/LPS treatment. Steroid anti-inflammatory agent (dexamethasone), histamine H1 receptor antagonists (diphenhydramine and pyrilamine), histamine H2 receptor antagonists (cimetidine and ranitidine) and 5-HT2 receptor antagonist (ketanserin) were effective in reducing the ALT level at 8 h after the treatment with GalN/LPS. Furthermore, dexamethasone, diphenhydramine and cimetidine inhibited the increase in hepatic HDC mRNA level. The increase in ALT level by GalN/LPS was much lower in mast cell-deficient mice than in the congenic normal mice. Diphenhydramine further inhibited ALT level in response to GalN/LPS in mast cell-deficient mice. Our data suggest that mast cells play an important role in the development of hepatic injury induced by GalN/LPS, and suggest that histamine and 5-HT released from mast cells and other cells are involved in this model.(Communicated by Masanori OTSUKA, M. J. A., June 10, 2003)