Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice.

Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice.
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DOI:
10.1084/jem.165.3.657
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发表时间:
1987-03-01
影响因子:
15.3
通讯作者:
GALANOS, C
GALANOS, C
中科院分区:
医学1区
文献类型:
--
作者:
LEHMANN, V;FREUDENBERG, MA;GALANOS, C

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研究了重组人肿瘤坏死因子(TNF)对内毒素过敏小鼠的毒性。用d -半乳糖胺处理的C3H/TifF小鼠对亚微克剂量TNF的致死效应敏感。在缺乏d -半乳糖胺的情况下,TNF在500微克时的致死率约为80%。在给予d -半乳糖胺后,对TNF的致敏持续时间长达8小时,对LPS的致敏持续时间长达4小时。与LPS一样,在给予d -半乳糖胺/TNF后长达2小时,尿苷可以抑制TNF的致敏,这表明肝脏中已知的对LPS致敏所必需的早期生化改变也是对TNF致敏所必需的。与LPS相比,TNF的毒性也在D-半乳糖胺处理的内毒素抗性C3H/HeJ小鼠中表达。这些小鼠对TNF的敏感性与内毒素敏感小鼠相同。在缺乏d -半乳糖胺的情况下,TNF在C3H/HeJ小鼠中的毒性与在C3H/TifF小鼠中获得的毒性相当,在500微克量级时是致命的。目前的结果支持TNF是内毒素致死毒性介质的假设。
The toxic properties of human recombinant tumor necrosis factor (TNF) were investigated in mice made hypersensitive to endotoxin by treatment with D-galactosamine. C3H/TifF mice treated with D-galactosamine were rendered sensitive to the lethal effects of submicrogram amounts of TNF. In the absence of D-galactosamine, TNF caused approximately 80% lethality with 500 micrograms. The duration of sensitization to TNF lasted up to 8 h after D-galactosamine administration, that towards LPS, up to 4 h. As with LPS, with TNF sensitization could be inhibited by uridine administered up to 2 h after D-galactosamine/TNF, showing that the early biochemical alterations in the liver known to be necessary for sensitization to LPS are also necessary for sensitization to TNF. In contrast to LPS, the toxicity of TNF was expressed also in D- galactosamine-treated endotoxin-resistant C3H/HeJ mice. The susceptibility of these mice to TNF was identical to that of endotoxin sensitive mice. In the absence of D-galactosamine the toxicity of TNF in C3H/HeJ mice was comparable to that obtained in C3H/TifF mice, being lethal with amounts of the order of 500 micrograms. The present results support the hypothesis that TNF is a mediator of lethal toxicity of endotoxin.
DOI: 10.1073/pnas.79.3.912
发表时间: 1982-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
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DOI: 10.1073/pnas.76.11.5939
发表时间: 1979-01-01
影响因子: 11.1
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DOI: 10.1084/jem.154.3.631
发表时间: 1981-01-01
影响因子: 15.3
作者:
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DOI: 10.1084/jem.163.6.1363
发表时间: 1986-06-01
期刊: The Journal of experimental medicine
影响因子: --
作者:
Nawroth PP;Bank I;Handley D;Cassimeris J;Chess L;Stern D
通讯作者: Stern D
DOI: 10.1126/science.3895437
发表时间: 1985-01-01
期刊: SCIENCE
影响因子: 56.9
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通讯作者: CERAMI, AC