Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo.

Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo.
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DOI:
10.4049/jimmunol.135.6.3972
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发表时间:
1985-12
影响因子:
4.4
通讯作者:
B. Beutler;I. Milsark;A. Cerami
B. Beutler;I. Milsark;A. Cerami
中科院分区:
医学2区
文献类型:
--
作者:
B. Beutler;I. Milsark;A. Cerami

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本研究采用高特异性放射受体法测定了家兔内毒素(LPS)诱导的激素分泌的时程。通过测量3 T3-L1细胞中的脂蛋白脂肪酶(LPL)抑制来监测相同血清样品中的Cachectin/TNF生物活性。不经Calmette Guérin、C. parvum或其它试剂。达到纳摩尔浓度的激素,在注射后2小时达到峰值水平;此后激素迅速清除。在单独的研究中,使用小鼠评估恶病质/TNF的分布和代谢结局。放射性碘标记的激素从血浆中清除,半衰期为6至7分钟。注射后标记物的组织分布研究表明,肝脏、肾脏、皮肤和胃肠道吸收了大部分激素。从注射动物中回收的组织的电泳分析表明,该激素在结合后非常迅速地降解。
A highly specific radioreceptor assay for cachectin/tumor necrosis factor (TNF) was utilized to measure the time course of lipopolysaccharide (LPS)-induced hormone production in rabbits. Cachectin/TNF bioactivity was monitored in the same serum samples by measuring lipoprotein lipase (LPL) suppression in 3T3-L1 cells. Cachectin/TNF is produced in large quantities by LPS-treated rabbits without priming by bacillus Calmette Guérin, C. parvum, or other agents. Nanomolar concentrations of the hormone are achieved, with peak levels occurring at 2 hr postinjection; the hormone is rapidly cleared thereafter. In separate studies, mice were used to assess the distribution and metabolic fate of cachectin/TNF. Radioiodinated hormone is cleared from the plasma with a half-life of 6 to 7 min. Studies of the tissue distribution of label after injection demonstrate that liver, kidneys, skin, and gastrointestinal tract take up most of the hormone. Electrophoretic analysis of tissues recovered from injected animals suggests that the hormone is very rapidly degraded after binding.