Defenestration of the sinusoidal endothelial cell in a rat model of cirrhosis.
We characterized the structural and immunohistological changes of sinusoidal endothelial cells that occur during cirrhosis in rats made cirrhotic with thioacetamide. Thioacetamide (200 mg/kg body wt) was injected intraperitoneally three times a week into male Wistar rats. Two, 4, 6 and 12 wk later, rat livers were observed under transmission and scanning electron microscopy and regular microscopy and immunostained with laminin and von Willebrand factor (factor VIII-related antigen) antibodies. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly after 2 wk in the thioacetamide-treated rats; however, they decreased within 4 wk after thioacetamide treatment. A basement membranelike structure in Disse's space was noted 6 wk after thioacetamide treatment. Laminin was detected in Disse's space after 4 wk. In vitro, in cultured sinusoidal endothelial cells, the diameter of sinusoidal endothelial fenestrations was significantly lower at 6 wk in thioacetamide-treated rats. von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 wk of thioacetamide treatment. These results suggest that as fibrosis develops in cirrhosis, the structural and immunohistochemical characteristics of sinusoidal endothelial cells change.
Mori
T
T
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Okanoue
T
T
Sawa
Y
Y
Hori
N
N
Ohta
M
M
Kagawa
K
K
D000818:Animals; D004727:Endothelium / Q000737:chemistry / Q000648:ultrastructure*; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000648:ultrastructure*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D014841:von Willebrand Factor / Q000032:analysis
D007797:Laminin; D014841:von Willebrand Factor