Biliary secretion of endotoxin and pathogenesis of primary biliary cirrhosis.
Previous studies suggested endotoxin, derived from the intestine through the portal blood to the liver, was predominantly metabolized by Kupffer cells. In the present study, fluorescent-labeled endotoxin injected into the rat portal vein was demonstrated not only in Kupffer cells but also in hepatocytes. Furthermore a great amount of labeled endotoxin was recovered in bile. In the livers of patients with primary biliary cirrhosis (PBC), immunohistochemistry demonstrated significant retention of endotoxin in the biliary epithelial cells, and treatment with ursodeoxycholic acid significantly reduced the retention in those cells. The study for detection of apoptosis demonstrated increased rates of apoptosis in hepatocytes and biliary epithelial cells in PBC liver, and the rate of apoptosis in biliary epithelial cells was significantly reduced after treatment with ursodeoxycholic acid. Immunohistochemistry in PBC liver demonstrated significant reduction of fluorescence intensity for a 7H6 antigen in biliary epithelial cells, indicating the increased paracellular permeability of bile ducts, because cellular immunolocalization of that antigen has been shown to be inversely correlated with the paracellular permeability of the tight junction. These results suggest that, in biliary epithelial cells, retention of endotoxin, increased apoptosis, and increased permeability of tight junctions may be involved in the pathogenesis of PBC.
Sakisaka
S
S
Second Department of Medicine, Kurume University School of Medicine, Japan. sakisaka@med.kurume-u.ac.jp
Koga
H
H
Sasatomi
K
K
Mimura
Y
Y
Kawaguchi
T
T
Tanikawa
K
K
D000818:Animals; D017209:Apoptosis; D001652:Bile Ducts / Q000293:injuries; D001659:Biliary Tract / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004731:Endotoxins / Q000378:metabolism* / Q000633:toxicity; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008105:Liver Cirrhosis, Biliary / Q000209:etiology* / Q000503:physiopathology; D051381:Rats
D004731:Endotoxins