Intrahepatic mast cells in chronic liver diseases

Abstract

Mast cells are known to be present in human liver but their distribution and density in normal livers and in chronic liver diseases have not previously been examined. In this study, we quantified mast cell numbers and examined their distribution in percutaneous biopsy specimens from normal livers (n = 8) and in two chronic progressive liver diseases: primary biliary cirrhosis (PBC) (n = 40) and alcoholic liver disease (n = 33). We compared differences in mast cell density between these two forms of chronic liver disease because it had been suggested that mast cells may play a role in the development of liver fibrosis, particularly in patients with chronic cholestatic liver disease who frequently have increased plasma histamine levels. Mast cells were identified by immunohistochemistry using a specific monoclonal antibody (AA1) raised against mast cell tryptase after an initial study showed this to be more sensitive for the detection of mast cells than the conventional histochemical stain, toluidine blue. Our results showed that small numbers of mast cells (3.9 ± 3.3/mm2) are present within the portal tracts and sinusoids of normal livers. In progressive chronic liver disease, increased numbers of mast cells were present, which correlated with the increasing amounts of liver fibrosis present. We found significantly more mast cells in the PBC group compared with the alcoholic group for a given amount of fibrosis. Our findings suggest that mast cells and their mediators may play a role in liver fibrogenesis. (HEPATOLOGY 1995; 22:1175–1181.).

Inhibition of mast cell-derived histamine secretion by cromolyn sodium treatment decreases biliary hyperplasia in cholestatic rodents

“…[48][49][50] Our present study focused primarily on the paracrine influence induced by mast cells on cholangiocytes; however, in data not shown here, we found that the proliferative response of hepatocytes was decreased in BDL þ cromolyn sodium-treated rats compared with BDL alone, and HSC activation is diminished after BDL þ cromolyn sodium treatment, suggesting that mast cell stabilization can also influence other liver cell types in vivo.…”

“…Histological analysis has demonstrated that mast cells are present in cirrhosis, fibrosis, hepatitis and cholangiopathies. 18,49,50 Mast cells are found in various areas of the liver depending upon the etiology. For example, and in support of our current findings, in both PSC and PBC, mast cells are found surrounding damaged bile ducts, portal triads and portal tracts.…”

“…For example, and in support of our current findings, in both PSC and PBC, mast cells are found surrounding damaged bile ducts, portal triads and portal tracts. 50,52 In hepatic fibrosis and hepatitis, mast cells are located near hepatic sinusoids and HSCs. 49 We found that mast cells were primarily adjacent to bile ducts, and as IBDM increased, hepatic mast cell numbers increased as shown by the positive correlation.…”

H3 histamine receptor agonist inhibits biliary growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2/ELK-1 pathway

“…[47][48][49] Indeed, some of those mediators like nitric oxide and cytokines have been shown to affect cholangiocyte biology. 50 Furthermore, in chronic liver diseases including PBC there is increased number of mast cells, 51 which causes a Figure 5 Measurement of the number of CK-19-positive cholangiocytes in liver sections from rats (that immediately after BDL) were treated with NaCl, RAMH, thioperamide maleate (H3R antagonist) or histamine in the absence or presence of thioperamide maleate for 1 week. In BDL rats, chronic RAMH administration induced a decrease in the number of CK-19-positive (see arrows) cholangiocytes compared to NaCl-treated rats.…”

“…51 Moreover, histamine serum levels are increased in patients with chronic cholestatic liver diseases. 52 Our findings are relevant to these cholangiopathies, as we have demonstrated that histamine, increased histamine serum levels and activation of H3R modulate the proliferative response of cholangiocytes to cholestasis.…”