A striking correlation between lethal activity and apoptotic DNA fragmentation of liver in response of D-galactosamine-sensitized mice to a non-lethal amount of lipopolysaccharide.
OBJECTIVE
To observe whether challenge of bacterial lipopolysaccharide (LPS) with D-galactosamine (D-GalN) in mice will result in apoptotic characteristic of vital organs.


METHODS
The experimental group of mice was challenged directly with bacterial LPS (0.05 microg) in the presence of D-GalN (20 mg), and the control group of mice was challenged either with bacterial LPS or with D-GalN alone. The organs including brain, kidney, heart, spleen, lung, and liver were removed at an indicated time point under ether anesthesia, and immediately homogenized, from which DNA was extracted. The DNA obtained from these organs was analyzed by agarose gel electrophoresis to determine whether the DNA laddering phenomenon existed. The amount of plasma LDH and GOT was detected in mice challenged with bacterial LPS in the presence of D-GalN, and either bacterial LPS or D-GalN alone.


RESULTS
Apoptotic DNA fragmentation was initially seen at 4 h after challenge only in the livers of mice challenged with bacterial LPS and D-GalN, all mice in this group challenged with bacterial LPS and D-GalN died at 7 h after challenge; in contrast, the animals in the control group were all alive and the DNA was integral.


CONCLUSIONS
The liver is the only specific target organ where apoptotic DNA fragmentation was present in mice treated with D-GalN and challenged with bacterial LPS and the liver impairment might be the critical cause of the lethality of mice elicited by bacterial LPS.
Zhou
Bing-Rong
BR
Max-Planck-Institute for Immunobiology, Stübeweg 51, D-79108 Freiburg i Br, Germany. bingrong_zhou@hotmail.com
Gumenscheimer
Marina
M
Freudenberg
Marina
M
Galanos
Chris
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001219:Aspartate Aminotransferases / Q000097:blood; D053938:DNA Fragmentation / Q000187:drug effects*; D005260:Female; D005688:Galactosamine / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D008070:Lipopolysaccharides; D005688:Galactosamine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases