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The D-Galactosamine Loaded Mouse and Its Enhanced Sensitivity to Lipopolysaccharide and Monophosphoryl Lipid A: A Role for Superoxide

 

作者: Gary Elliott,   Diane Welty,   Ya Kuo,  

 

期刊: Journal of Immunotherapy  (OVID Available online 1991)
卷期: Volume 10, issue 1  

页码: 69-74

 

ISSN:1524-9557

 

年代: 1991

 

出版商: OVID

 

关键词: Galactosamine;Monosphosphoryl lipid A;Lipopolysaccharide;Superoxide;Cu(II) (diisopropyl salicylate)2;Tumor necrosis factor

 

数据来源: OVID

 

摘要:

SummaryMice are relatively resistant to the lethal effects of endotoxin. Sensitivity to lipopolysaccharide (LPS) and monophosphoryl lipid A (MPL) can be enhanced by concurrently loading animals with D-galactosamine (D-gal). Significant diurnal variation in susceptibility to lethal toxicity was observed in D-gal loaded mice upon LPS or MPL immunostimulant challenge. In mice treated with either MPL or MPL plus D-gal, at the time of greatest toxic sensitivity, serum TNF levels were significantly higher than was seen in mice treated at a time of low sensitivity. Peritoneal exudate cells (PECs) harvested from mice treated with either D-gal or MPL displayed enhanced in vitro superoxide (SO) production. Simultaneous treatment with D-gal and MPL led to a synergistic enhancement of SO production above that induced by either xenobiotic alone. Pretreatment with the SO dismutase mimetic Cu(II) (diisopropyl salicylate)2 significantly protected mice from the lethal toxicity of Dgal- MPL challenge. PECs harvested from these same mice failed to display the elevated in vitro SO production reported above. SO elaboration in vivo, presumably by hepatocytes, PECs, and possibly other cells, subsequent to D-gal loading and LPS or MPL challenge, appears to play an important role in the lethal toxicity observed. The diurnal variation in toxicity reported in this animal model may result from TNF modulation of SO production in vivo.

 

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