Sinusoidal endothelial cell damage by activated macrophages in rat liver necrosis.
BACKGROUND
Massive hepatic necrosis caused by fibrin deposition in the hepatic sinusoids develops with hepatic macrophage activation in rats given endotoxin after administration of heat-killed Corynebacterium parvum. Targeted cells of such macrophages were investigated.


METHODS
In C. parvum-treated rats, the pathological appearance of liver cells was serially measured in serum following endotoxin administration and compared with the appearance in the perfusate during closed liver perfusion with endotoxin.


RESULTS
Serum activities of tumor necrosis factor, purine nucleoside phosphorylase present in both hepatocytes and sinusoidal endothelial cells, and levels of alanine aminotransferase were higher after 30 minutes, 1 hour, and 3 hours, respectively. Pretreatment of rats with gadolinium chloride, an inhibitor of macrophage function, reduced this liver injury. Although alanine aminotransferase activity remained almost unchanged in the liver perfusate, purine nucleoside phosphorylase activity increased. This increase was reduced when rats were pretreated with gadolinium chloride. There was sinusoidal endothelial cell damage around hepatic macrophages in the liver perfused with endotoxin.


CONCLUSIONS
Activated hepatic macrophages may cause sinusoidal endothelial cell damage leading to hepatocyte necrosis in rats given C. parvum and endotoxin.
Arai
M
M
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Mochida
S
S
Ohno
A
A
Ogata
I
I
Fujiwara
K
K
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D004727:Endothelium / Q000473:pathology; D004731:Endotoxins / Q000494:pharmacology; D008099:Liver / Q000473:pathology* / Q000648:ultrastructure; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D009336:Necrosis; D010477:Perfusion; D011425:Propionibacterium acnes / Q000502:physiology; D011683:Purine-Nucleoside Phosphorylase / Q000097:blood / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D011683:Purine-Nucleoside Phosphorylase; D000410:Alanine Transaminase