PRODUCTION OF TUMOR-NECROSIS-FACTOR IN UNPRIMED MICE - MECHANISM OF ENDOTOXIN-MEDIATED TUMOR NECROSIS

PRODUCTION OF TUMOR-NECROSIS-FACTOR IN UNPRIMED MICE - MECHANISM OF ENDOTOXIN-MEDIATED TUMOR NECROSIS
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DOI:
10.1016/s0171-2985(86)80064-x
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发表时间:
1986-07-01
期刊:
影响因子:
2.8
通讯作者:
GIFFORD, GE
GIFFORD, GE
中科院分区:
医学4区
文献类型:
--
作者:
FLICK, DA;GIFFORD, GE

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正常小鼠经脂多糖(LPS)注射后,血清中检测肿瘤坏死因子(TNF)含量。TNF的含量大约比小棒状杆菌引发的小鼠少200倍。未给予LPS的小鼠血清中未检测到TNF活性。TNF诱导的小鼠对反复给药内毒素不耐受,因此表现出耐受现象。在未引物的小鼠中产生的TNF类似于牛分枝杆菌,菌株bcg引物TNF在Sephacryl S-200和DEAE Sephacel柱上洗脱,并用兔抗血清培养成部分纯化的bcg引物TNF中和。7天龄皮下植入甲氧甲胺素A肿瘤的BALB/c小鼠给予TNF抗血清,内毒素诱导的出血性坏死在很大程度上被阻止。这些发现强烈提示内毒素诱导的肿瘤出血性坏死是通过TNF的产生和作用介导的。
Tumor necrosis factor (TNF) was detected in the sera of normal mice, unprimed by reticuloendothelial system (RES) stimulators, when such mice were injected with lipopolysaccharide (LPS). Amounts of TNF were approximately 200-fold less than those found in Corynebacterium parvum-primed mice. No TNF activity was detected in the sera of mice not administered LPS. TNF induction in unprimed mice was refractory to repeated administration of endotoxin, thus exhibiting a tolerance phenomenon. TNF produced in unprimed mice eluted similarly to Mycobacterium bovis, strain BCG-primed TNF on Sephacryl S-200 and DEAE Sephacel columns and was neutralized by rabbit antisera raised to partially purified BCG-primed TNF. When BALB/c mice having 7-day old subcutaneous Meth A tumor implants were administered TNF antiserum, endotoxin-induced hemorrhagic necrosis was largely prevented. These findings strongly suggest that endotoxin-induced hemorrhagic necrosis of tumors is mediated through TNF production and action.