The localization of lipopolysaccharide in an endotoxemic rat liver and its relation to sinusoidal thrombogenesis: light and electron microscopic studies.
The distribution of lipopolysaccharide (LPS) and sequential thrombus formation in the liver was investigated by immunohistochemical and cytochemical techniques in endotoxemic rats, using horseshoe crab factor C, a specific ligand for biologically active LPS, a monoclonal antibody against it, and rabbit anti-rat fibrinogen IgG. One hour after the intravenous administration of LPS (5 mg/kg), LPS was localized in the secondary lysosomes of Kupffer cells and in the vesicles of endothelial cells, mainly at the peripheries of the hepatic lobules. Small necrotic foci of hepatic tissue were scattered close to the LPS-containing Kupffer cells, and were frequently associated with infiltration of neutrophils and deposition of fibrin. Three hours after the administration of LPS, the immunohistochemical reaction of LPS became stronger and was mostly confined to Kupffer cells. Strands of polymerized fibrin were frequently observed on both the surface of the LPS-containing Kupffer cells and on endothelial cells. These findings suggest that the activation of the coagulation cascade in plasma is first initiated, even though only transiently, by hepatic necrosis which is probably caused by LPS-activated leukocytes, and then by the procoagulant activity expressed on the surface of both Kupffer cells and endothelial cells. Fibrinogen-related antigens were also immuno-ultrastructurally detected in the lysosomes of Kupffer cells three hours after the injection of LPS, which suggested that the Kupffer cells phagocytozed and degraded fibrin. Therefore Kupffer cells in endotoxemia may closely participate in both the sinusoidal thrombogenesis and degradation of fibrin.
Takeuchi
M
M
Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nakashima
Y
Y
Miura
Y
Y
Nakagawa
K
K
Uragoh
K
K
Iwanaga
S
S
Hori
Y
Y
Sueishi
K
K
D000818:Animals; D000941:Antigens / Q000032:analysis; D060829:Arthropod Proteins; D004731:Endotoxins / Q000097:blood*; D004792:Enzyme Precursors; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D012697:Serine Endopeptidases; D013927:Thrombosis / Q000209:etiology*; D013997:Time Factors; D014018:Tissue Distribution
D000941:Antigens; D060829:Arthropod Proteins; D004731:Endotoxins; D004792:Enzyme Precursors; D005338:Fibrin Fibrinogen Degradation Products; D008070:Lipopolysaccharides; C023456:fibrinogen-related antigen; D012697:Serine Endopeptidases; C057151:Limulus clotting factor C