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Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosis
Author(s) -
Kinnman Nils,
Lindblad Anders,
Housset Chantal,
Buentke Eva,
Scheynius Annika,
Strandvik Birgitta,
Hultcrantz Rolf
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.9111
Subject(s) - cystic fibrosis transmembrane conductance regulator , pathology , cystic fibrosis , bile duct , intrahepatic bile ducts , immunohistochemistry , fibrosis , hepatic stellate cell , biology , inflammation , bile duct diseases , biliary tract , medicine
The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule‐1 (ICAM‐1) and liver cell‐type markers in liver cryosections in 11 patients with CF‐associated liver disease, and non‐CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM‐1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile‐duct epithelial cells in patients carrying the ΔF508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of ΔF508 CFTR processing in intrahepatic biliary epithelium. ICAM‐1 expression on bile‐duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF‐associated liver disease.