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.
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
T
T
Mori
T
T
Okanoue
Y
Y
Sawa
N
N
Hori
M
M
Ohta
K
K
Kagawa
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