Apoptotic cell death in the response of D-galactosamine-sensitized mice to lipopolysaccharide as an experimental endotoxic shock model.
The apoptotic cell death induced in D-galactosamine-sensitized mice by administration of lipopolysaccharide was characterized. Administration of lipopolysaccharide caused apoptotic cell death in livers of D-galactosamine-sensitized mice. Apoptotic cells were also detected in the kidney, thymus, spleen, and lymph node. Severe hepatic apoptosis in D-galactosamine-sensitized mice was reproduced by transfer of the sera from mice injected with D-galactosamine and lipopolysaccharide. The hepatocyte apoptosis induced by lipopolysaccharide was completely prevented by an anti-tumor necrosis factor alpha antibody but not by an anti-gamma interferon antibody. Administration of recombinant tumor necrosis factor into D-galactosamine-sensitized mice also caused hepatocyte apoptosis. Lipopolysaccharide-induced hepatocyte apoptosis in D-galactosamine-sensitized mice did not seem to be mediated by Fas antigen. It was suggested that lipopolysaccharide- induced hepatic injury and failure in D-galactosamine-sensitized mice was due to the apoptotic cell death of hepatocytes caused by tumor necrosis factor alpha released in the circulation.
Morikawa
A
A
Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Japan.
Sugiyama
T
T
Kato
Y
Y
Koide
N
N
Jiang
G Z
GZ
Takahashi
K
K
Tamada
Y
Y
Yokochi
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005688:Galactosamine / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D012772:Shock, Septic / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D004247:DNA