Role of adhesion between activated macrophages and endothelial cells in the development of two types of massive hepatic necrosis in rats.
Sinusoidal endothelial cell damage is produced by activation of hepatic macrophages after endotoxin administration in rats pretreated with Cornyebacterium parvum or undergoing 70% hepatectomy. Such damage causes fibrin deposition in the hepatic sinusoids leading to massive hepatic necrosis. In the C. parvum model, cytotoxic mediators, such as tumour necrosis factor (TNF)alpha and superoxide anions released from activated hepatic macrophages directly destroy sinusoidal endothelial cells. In contrast, in the partial hepatectomy model, endothelial cell damage occurs as a result of fibrin deposition due to derangement of the coagulation equilibrium regulated by tissue factor and thrombomodulin expressed on hepatic macrophages and sinusoidal endothelial cells, respectively. Immunohistological examination revealed that the expression of ICAM-1 in sinusoidal endothelial cells and LFA-1 in hepatic macrophages was greater in both models than in normal rats preceding the development of hepatic necrosis. The extent of liver injury was significantly attenuated by treatment with monoclonal antibodies against both adhesion molecules in the C. parvum model, but aggravated in the partial hepatectomy model, compared to control rats. We conclude that adhesion of activated macrophages to endothelial cells via LFA-1 and ICAM-1 in the hepatic sinusoids is essential for endothelial cell destruction in the C. parvum model, but can act protectively against provocation of fibrin deposition in the hepatectomy model.
Mochida
S
S
Third Department of Internal Medicine, Saitama Medical School, Japan.
Ohno
A
A
Arai
M
M
Fujiwara
K
K
D000818:Animals; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000502:physiology*; D004731:Endotoxins / Q000008:administration & dosage; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000166:cytology; D009336:Necrosis; D011425:Propionibacterium acnes; D051381:Rats; D011916:Rats, Inbred F344
D004731:Endotoxins; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1