Role of adhesion molecules in the development of massive hepatic necrosis in rats.
Massive hepatic necrosis develops after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes as a result of microcirculatory disturbance caused by endothelial cell destruction by activated macrophages in the hepatic sinusoids. Immunohistochemical hepatic expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen 1 alpha (LFA-1 alpha) and the effect of monoclonal antibodies against both adhesion molecules on liver necrosis provoked after endotoxin administration was studied in these rats. There were increased stains of ICAM-1 in endothelial cells and LFA-1 alpha in macrophages in the hepatic sinusoids in Propionibacterium acnes-pretreated rats compared with normal rats. Such stains were further increased soon after endotoxin administration, followed by development of hepatic necrosis. Monoclonal antibodies against both adhesion molecules significantly attenuated the extent of liver injury compared with controls, without affecting the infiltration and activation of hepatic macrophages. Polyclonal antibodies against polymorphonuclear leukocytes eradicated circulating neutrophils, but did not change such liver injury, although gum arabic, which suppressed macrophage activation, attenuated the extent of liver injury. Thus, adhesion between endothelial cells and activated macrophages in the hepatic sinusoids via ICAM-1 and LFA-1 alpha is essential for the initiation of massive hepatic necrosis of this type. Contribution of neutrophils seems less likely.
Mochida
S
S
Third Department of Internal Medicine, Saitama Medical School, Japan.
Ohno
A
A
Arai
M
M
Tamatani
T
T
Miyasaka
M
M
Fujiwara
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion; D002465:Cell Movement; D004731:Endotoxins / Q000633:toxicity; D006170:Gum Arabic / Q000494:pharmacology; D007106:Immune Sera / Q000276:immunology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D009336:Necrosis; D009504:Neutrophils / Q000276:immunology; D011425:Propionibacterium acnes / Q000502:physiology; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344
D000906:Antibodies; D004731:Endotoxins; D007106:Immune Sera; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D006170:Gum Arabic