Endothelial cell transformation in primary biliary cirrhosis: a morphological and biochemical study.
There is increasing interest in the changes of the endothelial lining of the hepatic sinusoids during the development of chronic liver disease. In this study we looked for evidence of hepatic sinusoidal endothelial cell transformation and basement membrane production in patients with primary biliary cirrhosis. Morphological transformation to vascular-type endothelial cells, as evidenced by the development VIII-related antigen, was seen at the interface between portal tracts or fibrous septae and hepatic parenchyma; the most marked changes were observed in patients with established cirrhosis. Increased immunohistochemical staining for the basement membrane components type IV collagen and laminin was also found in a similar distribution. Raised serum levels of hyaluronic acid, a glycosaminoglycan metabolized by normal hepatic endothelial cells, were found in most patients and correlated strongly with advancing histological stage. Furthermore, significant positive correlations were found between serum hyaluronic acid and serum levels of laminin and type IV collagen. The unique structure of the normal endothelial lining of the hepatic sinusoids is important in the maintenance of hepatic function. Our data show that significant changes in endothelial cell structure and function occur in primary biliary cirrhosis and appear to be a contributing factor to the progression of the disease. Further studies are needed to determine the extent and importance of these changes in other forms of chronic liver disease.
Babbs
C
C
University Department of Gastroenterology, Manchester Royal Infirmary, England.
Haboubi
N Y
NY
Mellor
J M
JM
Smith
A
A
Rowan
B P
BP
Warnes
T W
TW
D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000378:metabolism / Q000473:pathology*
D006820:Hyaluronic Acid