Mechanism of calcium ionophore A23187-induced priming of bone marrow-derived macrophages for tumor cell killing: relationship to priming by interferon.
Mechanism of calcium ionophore A23187-induced priming of bone marrow-derived macrophages for tumor cell killing: relationship to priming by interferon.
复制标题
钙离子载体 A23187 诱导骨髓源性巨噬细胞启动杀死肿瘤细胞的机制：与干扰素启动的关系。
DOI：
10.1073/pnas.82.17.5959
复制
发表时间：
1985
影响因子：
11.1
通讯作者：
Torres,BA
中科院分区：
文献类型：
--
作者：
Johnson,HM;Torres,BA
干扰素通过使巨噬细胞对脂多糖等触发剂敏感，为杀伤肿瘤细胞启动巨噬细胞。为了确定启动信号的性质，我们测试了佛波12-肉豆酸13-醋酸酯、二酰基甘油、血小板活化因子、花生四烯酸、白三烯B4和钙离子载体A23187激活小鼠骨髓源性巨噬细胞以杀死P815肥大细胞瘤靶细胞的能力。离子载体A23187是唯一能够取代干扰素启动信号的物质。A23187的启动似乎部分归因于巨噬细胞培养中干扰素α / β的诱导，因为其作用部分但特异性地被干扰素α / β抗体阻断。与此一致的观察结果是，A23187诱导巨噬细胞培养中α / β干扰素的产生。A23187的启动并未被干扰素抗体完全逆转，说明与干扰素诱导无关的因素也在巨噬细胞的启动中发挥作用。肉豆蔻酸酯或二酰基甘油不能激活巨噬细胞杀死肿瘤细胞，这表明蛋白激酶C的激活不足以启动巨噬细胞。因此，A23187似乎通过干扰素和非干扰素诱导的联合机制为巨噬细胞杀伤提供了启动信号。
Interferon primes macrophages for tumor cell killing by rendering them sensitive to triggering agents such as lipopolysaccharide. In an attempt to determine the nature of the priming signal, we tested phorbol 12-myristate 13-acetate, diacylglycerol, platelet-activating factor, arachidonic acid, leukotriene B4, and the calcium ionophore A23187 for their ability to prime mouse bone marrow-derived macrophages for activation to kill P815 mastocytoma target cells. The ionophore A23187 was the only substance that was able to replace the interferon priming signal. A23187 priming appeared to be due in part to induction of interferon alpha/beta in the macrophage cultures, since its effect was partially but specifically blocked by antibody to interferon alpha/beta. Consistent with this was the observation that A23187 induced interferon alpha/beta production in macrophage cultures. The fact that A23187 priming was not completely reversed by antibody to interferon would suggest that factors unrelated to interferon induction also played a role in macrophage priming. The failure of phorbol myristate acetate or diacylglycerol to prime macrophages for tumor cell killing would suggest that activation of protein kinase C is not sufficient for priming. Thus, A23187 appears to provide the priming signal for macrophage killing through the combination of interferon- and non-interferon-induced mechanisms.