ACTIVATED MACROPHAGES KILL TUMOR-CELLS BY RELEASING ARGINASE

ACTIVATED MACROPHAGES KILL TUMOR-CELLS BY RELEASING ARGINASE
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DOI:
10.1038/273758a0
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发表时间:
1978-01-01
期刊:
影响因子:
64.8
通讯作者:
CURRIE, GA
CURRIE, GA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
CURRIE, GA

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当啮齿动物腹腔渗出物巨噬细胞暴露于酵母聚糖、细菌脂多糖 (LPS) 或淋巴因子等刺激物时,它们会对各种培养的靶细胞产生细胞毒性 1,2。这种“激活”巨噬细胞的毒性作用没有表现出免疫特异性,但可能对转化细胞或恶性细胞表现出广泛的选择性。此外,这种细胞毒性活性归因于可溶性巨噬细胞产物。 Kunget等人已经证明,向小鼠混合白细胞培养物中添加过量的巨噬细胞会耗尽培养基中的精氨酸,从而抑制淋巴细胞反应性。这与培养的巨噬细胞中精氨酸酶的出现有关。这里报道的实验表明,酵母聚糖或脂多糖激活巨噬细胞会诱导精氨酸酶的产生和释放,并且巨噬细胞及其上清液介质对靶细胞的细胞毒性活性是精氨酸剥夺的结果。
WHEN rodent peritoneal exudate macrophages are exposed to stimuli such as zymosan, bacterial lipopolysaccharide (LPS) or lymphokines they become cytotoxic to a variety of cultured target cells1,2. The toxic effects of such ‘activated’ macrophages show no immunological specificity but may show a broad selectivity for transformed3or malignant cells4. Furthermore, this cytotoxic activity has been attributed4to a soluble macro-phage product. Kunget al.have shown5that the addition of excess macrophages to mouse mixed leukocyte cultures depletes the culture medium of arginine and thereby suppresses lymphocyte reactivity. This is associated with the appearance of arginase within cultured macrophages. The experiments reported here show that activation of macrophages by zymosan or LPS induces the production and release of arginase and that the cytotoxic activity of the macrophages and of their supernatant media on the target cells is a consequence of arginine deprivation.