Bile duct cells in primary biliary cirrhosis are 'primed' for apoptosis.
OBJECTIVE
Primary biliary cirrhosis (PBC) is characterized by progressive, immune-mediated destruction of bile ducts (<75 microm diameter) and secondary changes related to cholestasis which may involve apoptosis. In this study we sought to examine the protein expression of genes involved in apoptosis in biliary epithelium of PBC cases.


METHODS
In order to investigate the susceptibility of biliary epithelial cells to apoptosis and their ability to proliferate, we examined the expression of a number of apoptosis related proteins in early and late stage PBC and histologically normal liver control tissue using immunohistochemistry.


METHODS
Liver biopsies from 15 early (stages I and II) and 14 late (stages III and IV) cases of PBC and 15 normal cases were examined immunohistochemically for expression of p53, CD95/Fas, bax, bcl-x, bcl-2 and the proliferation marker Ki-67.


RESULTS
CD95/Fas, bax and bcl-x were identified in biliary epithelium in 8/15, 11/15 and 8/15 normal biopsies. Weak expression of bcl-2 was found, but p53 was not identified. In cases of PBC surviving bile ducts showed strong bax and bcl-x expression. Inflammatory infiltrates were strongly bcl-2 positive. In cases showing a marked ductular reaction there was increased reactivity for bax and bcl-x in ductules. No change in CD95/Fas or p53 expression was seen. An increase in Ki-67 positive biliary epithelial cells was seen in PBC cases, indicating cell cycle activity.


CONCLUSIONS
Bile duct epithelium constitutively expresses several genes involved in the execution of apoptosis but these cells also retain the ability to proliferate.
Graham
A M
AM
University Department of Pathology, Edinburgh, UK. ag@srv4.med.ed.ac.uk
Dollinger
M M
MM
Howie
S E
SE
Harrison
D J
DJ
D017209:Apoptosis / Q000235:genetics; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology*; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor