TUMOR-NECROSIS-FACTOR - A POTENT EFFECTOR MOLECULE FOR TUMOR-CELL KILLING BY ACTIVATED MACROPHAGES
TUMOR-NECROSIS-FACTOR - A POTENT EFFECTOR MOLECULE FOR TUMOR-CELL KILLING BY ACTIVATED MACROPHAGES
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DOI：
10.1073/pnas.83.14.5233
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发表时间：
1986-07-01
影响因子：
11.1
通讯作者：
SCHREIBER, H
中科院分区：
文献类型：
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作者：
URBAN, JL;SHEPARD, HM;SCHREIBER, H
活化巨噬细胞(aM.Phi.)比正常细胞更有效地摧毁癌细胞。巨噬细胞摧毁癌细胞的机制尚不清楚。我们在此报道，重组(R)型肿瘤坏死因子α可杀死对苯丙氨酸分枝杆菌敏感的肿瘤细胞。(肿瘤坏死因子-α)，而对甲氧西林耐药的变异型肿瘤细胞经体外或体内筛选后，对重组肿瘤坏死因子-α具有杀伤作用。对rTNF-α抗性变异体的反向选择导致细胞也能抵抗M.PHI的杀伤。巨噬细胞耐药变异体对其他杀瘤细胞或可溶性介质的敏感性没有改变，只是抗巨噬细胞变异体对另一种细胞毒蛋白B细胞淋巴毒素的作用也有抵抗力，B细胞淋巴毒素在结构上与rTNF-α相关。无论是测量aM.PHI的短期或长期细胞毒性效应，都得到了类似的结果。最后，结果表明，小鼠aM.PHI对肿瘤细胞的杀伤可被一种多克隆抗体完全抑制，该多克隆抗体中和了小鼠肿瘤坏死因子-α的作用。这些结果表明了肿瘤坏死因子-α的主要作用。在体内外对肿瘤细胞的杀灭作用。
Activated macrophages (aM.PHI.) destroy more effectively cancer cells than normal cells. The mechanism by which macrophages destroy cancer cells is not known. We report here that tumor cells susceptible to aM.PHI. were killed by recombinant (r) tumor necrosis factor type .alpha. (TNF-.alpha.), whereas variant tumor cells resistant to aM.PHI. after selection in vitro or in vivo were resistant to killing by rTNF-.alpha.. The converse selection for rTNF-.alpha.-resistant variants resulted in cells that were also resistant to killing by aM.PHI.. The sensitivity of macrophage-resistant variants was not changed to other tumoricidal cells or soluble mediators, except that the macrophage-resistant variants were also resistant to the effects of another cytotoxic protein, B-cell lymphotoxin, which is structurally related to rTNF-.alpha.. Similar results were obtained regardless of whether short-term or long-term cytotoxic effects of aM.PHI. were measured. Finally, it was shown that killing of tumor cells by murine aM.PHI. was completely inhibited with a polyclonal antibody that neutralizes the effects of murine TNF-.alpha.. These results suggest a major role for TNF-.alpha. in tumor cell destruction by aM.PHI. in vitro and in vivo.