Aberrant expression of stem cell factor on biliary epithelial cells and peribiliary infiltration of c-kit-expressing mast cells in hepatolithiasis and primary sclerosing cholangitis: a possible contribution to bile duct fibrosis.
Hepatolithiasis and primary sclerosing cholangitis (PSC) are intractable chronic biliary diseases. In hepatolithiasis, bilirubin-calcium stones are packed in multiple irregularly dilated intrahepatic bile ducts. In PSC, small bilirubin-calcium stones develop terminally. The progressive periductal fibrosis with dilated and stenotic bile ducts in these two diseases may play a role in their incurability. This immunohistochemical study has investigated the expression of some factors that might be involved in fibrogenesis in hepatolithiasis and PSC. Many mast cells positive for c-kit were found in the periductal and ductal fibrosis around the intrahepatic large bile ducts and also around the proliferative peribiliary glands. These mast cells also expressed basic fibroblast growth factor and/or tumour necrosis factor-alpha, which are known as fibrogenetic factors. It was of interest that the aberrant expression of stem cell factor (SCF), a ligand of c-kit, was demonstrated on biliary epithelia of the dilated and stenotic bile ducts showing periductal fibrosis and inflammation and also of the proliferated peribiliary glands in hepatolithiasis and PSC, while no such expression was seen in non-affected bile ducts in hepatolithiasis or in the bile ducts in normal livers. Some of the infiltrating mononuclear cells around the SCF-expressing bile ducts were also positive for SCF. It seems likely that aberrantly expressed SCF on biliary epithelial cells accumulates and stimulates mast cells via the c-kit receptor and that these up-regulated mast cells induce progressive periductal and portal fibrosis by displaying fibrogenetic factors in hepatolithiasis and PSC.
Tsuneyama
K
K
Second Department of Pathology, Kanazawa University School of Medicine, Kanazawa 920, Japan.
Kono
N
N
Yamashiro
M
M
Kouda
W
W
Sabit
A
A
Sasaki
M
M
Nakanuma
Y
Y
D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D015209:Cholangitis, Sclerosing / Q000378:metabolism*; D002769:Cholelithiasis / Q000378:metabolism*; D053818:Chymases; D004847:Epithelial Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000032:analysis; D019089:Stem Cell Factor / Q000378:metabolism*; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases