ENDOTOXIN-INDUCED SERUM FACTOR THAT CAUSES NECROSIS OF TUMORS

ENDOTOXIN-INDUCED SERUM FACTOR THAT CAUSES NECROSIS OF TUMORS
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DOI:
10.1073/pnas.72.9.3666
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发表时间:
1975-01-01
影响因子:
11.1
通讯作者:
WILLIAMSON, B
WILLIAMSON, B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CARSWELL, EA;OLD, LJ;WILLIAMSON, B

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在研究由内毒素引起的肿瘤的"出血性坏死"时,发现用内毒素处理的卡介苗(BCG)感染的小鼠的血清含有一种物质(肿瘤坏死因子; TNF),其模拟内毒素本身的肿瘤坏死作用。TNF阳性血清在引起甲硫氨酸肉瘤和其他移植肿瘤坏死方面与内毒素本身一样有效。多种试验表明,TNF不是残留的内毒素,而是内毒素从宿主细胞(可能是巨噬细胞)释放的因子。棒状杆菌和酵母多糖,像BCG一样诱导网状内皮系统的增生,可以替代BCG在引发小鼠中通过内毒素释放TNF。TNF在体外对两种肿瘤细胞系有毒性;对小鼠胚胎培养物无毒性。我们提出TNF介导内毒素诱导的肿瘤坏死,并且它可能是由活化的巨噬细胞抑制转化细胞的原因。
In studying "hemorrhagic necrosis" of tumors produced by endotoxin, it was found that the serum of bacillus Calmette--Guerin (BCG)-infected mice treated with endotoxin contains a substance (tumor necrosis factor; TNF) which mimics the tumor necrotic action of endotoxin itself. TNF-positive serum is as effective as endotoxin itself in causing necrosis of the sarcoma Meth A and other transplanted tumors. A variety of tests indicate that TNF is not residual endotoxin, but a factor released from host cells, probably macrophages, by endotoxin. Corynebacteria and Zymosan, which like BCG induce hyperplasia of the reticulo-endothelial system, can substitute for BCG in priming mice for release of TNF by endotoxin. TNF is toxic in vitro for two neoplastic cell lines; it is not toxic for mouse embryo cultures. We propose that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.