Marked changes of the hepatic sinusoid in a transgenic mouse model of acute immune-mediated hepatitis.
OBJECTIVE
The liver sinusoidal endothelial cell (LSEC) is increasingly recognized as having an important role in hepatic immunity. However, the responses of LSECs and the hepatic sinusoid in immune-mediated hepatitis are poorly described.


METHODS
We studied a transgenic mouse model of acute immune-mediated hepatitis: Met-Kb mice injected with T cells from Des-TCR mice.


RESULTS
Hepatitis was characterized by lymphocyte infiltrates causing severe but transient liver damage. There were marked changes in the ultrastructure of the LSEC five days after injection of the T cells that coincided with the peak of the hepatitis. The porosity of fenestrations in the LSEC decreased and the endothelium became thickened. LSECs appeared to be markedly activated. These changes were associated with narrowing of the space of Disse, loss of hepatocellular microvilli and deposition of basal lamina. Lymphocytes were seen passing through fenestrations. Loss of fenestration in the LSEC prevented hepatitis induced by a second injection of lymphocytes on day 5.


CONCLUSIONS
Structural changes in the LSEC occur during the peak of a mouse model of immune-mediated hepatitis. These changes were associated with attenuation of subsequent liver damage, suggesting that they may influence immunological responses mediated by LSECs or the passage of lymphocytes through LSEC fenestrations.
Warren
Alessandra
A
Centre for Education and Research on Ageing and the ANZAC Research Institute, Concord RG Hospital and University of Sydney, Sydney, Australia.
Bertolino
Patrick
P
Benseler
Volker
V
Fraser
Robin
R
McCaughan
Geoffrey W
GW
Le Couteur
David G
DG
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000648:ultrastructure; D006183:H-2 Antigens / Q000235:genetics; D019693:Hepatitis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D022781:Hepatocytes / Q000648:ultrastructure*; D008099:Liver / Q000276:immunology* / Q000648:ultrastructure*; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D011948:Receptors, Antigen, T-Cell