Comparative effects of various classes of mouse interferons on macrophage activation for tumor cell killing.
Comparative effects of various classes of mouse interferons on macrophage activation for tumor cell killing.
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DOI：
10.4049/jimmunol.134.2.977
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发表时间：
1985-02
影响因子：
4.4
通讯作者：
J. Pace;S. Russell;P. A. Leblanc;D. Murasko
中科院分区：
文献类型：
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作者：
J. Pace;S. Russell;P. A. Leblanc;D. Murasko
在包括或不含可检测内毒素的条件下，通过使用来自C3 H/HeN和C3 H/HeJ小鼠的蛋白酶胨诱导的腹腔巨噬细胞，测定小鼠干扰素-α（MuIFN-α）、-β（MuIFN-β）和-γ（MuIFN-γ）对巨噬细胞活化以杀死肿瘤细胞的作用。在所使用的条件下，单独的干扰素都不能直接激活巨噬细胞杀死肿瘤细胞。然而，通过污染内毒素、添加的细菌脂多糖（LPS）或热灭活的单核细胞增生李斯特菌（HKLM）向响应性巨噬细胞提供第二信号，所有三种类型的干扰素诱导细胞溶解活性，MuIFN-γ的活性比MuIFN-α或β高约500至1000倍。因此，所有三种干扰素都能够引发巨噬细胞的杀伤，但在细胞溶解活性表达之前需要第二个信号。当MuIFN-γ与MuIFN-α或MuIFN-β混合并置于巨噬细胞上时，几乎没有或没有产生杀伤作用。然而，与单独用MuIFN-γ处理的巨噬细胞相比，MuIFN-γ与MuIFN-α或MuIFN-β的混合物确实增加了巨噬细胞对LPS触发的敏感性。这些结果总体上是重要的，因为它们i）证实了在各种干扰素之间就其引发巨噬细胞以杀死肿瘤细胞的能力而言存在显著的定量差异; ii）表明为了成为有效的激活剂，每种类型的干扰素必须与第二刺激物如LPS或HKLM组合; iii）显示MuIFN-α和β都不能为由MuIFN-γ引发的巨噬细胞提供有效的第二触发信号;和iv）证明MuIFN-γ与MuIFN-α或MuIFN-β的混合物与单独使用的任何一种干扰素相比在诱导引发方面最有效。
The effects of mouse interferon-alpha (MuIFN-alpha), -beta (MuIFN-beta), and -gamma (MuIFN-gamma) on macrophage activation for tumor cell killing were determined by using proteose peptone-elicited peritoneal macrophages from C3H/HeN and C3H/HeJ mice under conditions that either included or were free of detectable endotoxin. Alone, under the conditions used, none of the interferons was able to activate macrophages directly for tumor cell killing. However, with a second signal provided to responsive macrophages by contaminating endotoxin, added bacterial lipopolysaccharide (LPS), or heat-killed Listeria monocytogenes (HKLM), all three types of interferon induced cytolytic activity, with MuIFN-gamma approximately 500 to 1000-fold more active than either MuIFN-alpha or -beta. Thus, all three interferons were able to prime macrophages for killing but required a second signal before cytolytic activity could be expressed. When MuIFN-gamma was mixed with either MuIFN-alpha or -beta and placed on macrophages, little or no killing developed. Mixtures of MuIFN-gamma with either MuIFN-alpha or -beta did increase the sensitivity of macrophages to triggering by LPS, however, compared with macrophages treated with MuIFN-gamma alone. The results are collectively important because they i) confirm that significant quantitative differences exist between the various interferons with regard to their capacity to prime macrophages for tumor cell killing; ii) indicate that to be an efficient activator each type of interferon must be combined with a second stimulus, such as LPS or HKLM; iii) show that neither MuIFN-alpha nor -beta can provide an efficient second triggering signal for macrophages that are primed by MuIFN-gamma; and iv) document that mixtures of MuIFN-gamma with either MuIFN-alpha or -beta are most efficient at inducing priming, compared with any one of the interferons used alone.