INDUCTION OF MACROPHAGE TUMORICIDAL ACTIVITY BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

INDUCTION OF MACROPHAGE TUMORICIDAL ACTIVITY BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR
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DOI:
10.1126/science.3083507
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发表时间:
1986-04-25
期刊:
影响因子:
56.9
通讯作者:
CONLON, PJ
CONLON, PJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
GRABSTEIN, KH;URDAL, DL;CONLON, PJ

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单核细胞是外周血白细胞的一个亚群,当被免疫系统的调节激素适当激活时,能够成为巨噬细胞--对肿瘤和寄生虫的免疫反应的强大效应细胞。克隆了T淋巴细胞源性淋巴因子的互补DNA粒细胞-巨噬细胞集落刺激因子(GM-CSF),并在酵母中表达并纯化了重组GM-CSF蛋白。纯化的重组人GM-CSF在体外刺激外周血单核细胞对恶性黑色素瘤细胞株A375产生细胞毒作用。另一种T细胞衍生的淋巴因子--γ-干扰素(干扰素-γ)也刺激外周血单核细胞对这种恶性细胞系形成肿瘤。当干扰素-γ。激活单核细胞成为杀瘤细胞,需要外源性添加的脂多糖的额外刺激。GM-CSF激活单核细胞不需要这种外源信号。
Monocytes are a subpopulation of peripheral blood leukocytes, which when appropriately activated by the regulatory hormones of the immune system, are capable of becoming macrophages-potent effector cells from immune response to tumors and parasites. A complementary DNA for the T lymphocyte-derived lymphokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), has been cloned, and recombinant GM-CSF protein has been expressed in yeast and purified to homogeneity. This purified human recombinant GM-CSF stimulated peripheral blood monocytes in vitro to become cytotoxic for the malignant melanoma cell line A375. Another T cell-derived lymphokine, .gamma.-interferon (IFN-.gamma.), also stimulated peripheral blood monocytes to become tumoricial against this malignant cell line. When IFN-.gamma. activates monocytes to become tumoricidal, additional stimulation by exogenously added lipopolysaccharide is required. No such exogenous signals were required for the activation of monocytes by GM-CSF.