MODULATION OF TUMORICIDAL ACTIVITY, INDUCED IN BONE-MARROW-DERIVED MONONUCLEAR PHAGOCYTES BY INTERFERON-GAMMA OR CORYNEBACTERIUM-PARVUM, BY INTERFERON-BETA, TUMOR-NECROSIS-FACTOR, PROSTAGLANDIN-E(2), AND TRANSFORMING GROWTH-FACTOR-BETA
MODULATION OF TUMORICIDAL ACTIVITY, INDUCED IN BONE-MARROW-DERIVED MONONUCLEAR PHAGOCYTES BY INTERFERON-GAMMA OR CORYNEBACTERIUM-PARVUM, BY INTERFERON-BETA, TUMOR-NECROSIS-FACTOR, PROSTAGLANDIN-E(2), AND TRANSFORMING GROWTH-FACTOR-BETA
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DOI：
10.1002/ijc.2910490526
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发表时间：
1991-11-11
影响因子：
6.4
通讯作者：
VANDERMEIDE, PH
中科院分区：
文献类型：
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作者：
KELLER, R;KEIST, R;VANDERMEIDE, PH
在一系列的代理商，包括各种白细胞介素和生长因子，只有干扰素-γ（IFN-γ）和热杀死的棒状杆菌（CP）的有机体能够引起，在24小时内，在骨髓来源的单核细胞（BMM）吞噬细胞的杀肿瘤活性。在随后的实验中，比较了干扰素-β（IFN-β）、肿瘤坏死因子-α（TNF-α）、前列腺素E2（PGE 2）和转化生长因子-β（TGF-β）单独或2种的组合调节IFN-γ或CP在BMM吞噬细胞中触发的杀肿瘤活性的能力。在生理条件下由巨噬细胞分泌的浓度中，这些药剂被证明在调节杀肿瘤活性的诱导和/或表达方面是有效的。然而，它们干扰杀肿瘤活性的能力变化很大，这取决于巨噬细胞分化和/或功能反应的程度，巨噬细胞活化的途径，巨噬细胞分泌分子的类型、浓度和组合，以及药剂是否存在于诱导和表达期间或仅存在于杀肿瘤活性的表达期间。在显示IFN-β和TNF-α主要是增强和TGF-β主要是抑制，而PGE 2抑制诱导，但增强表达的杀肿瘤活性，我们的研究结果提供了进一步支持的概念，这些巨噬细胞衍生的分子在巨噬细胞的功能活动的自分泌调节的关键作用。
Among a series of agents, including various interleukins and growth factors, only interferon-gamma (IFN-gamma) and heat-killed Corynebacterium parvum (CP) organisms were able to elicit, within 24 hr, tumoricidal activity in bone-marrow-derived mononuclear (BMM) phagocytes. In subsequent experiments, the abilities of interferon-beta (IFN-beta), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2), and transforming growth factor-beta (TFG-beta), alone or in combinations of 2, to modulate tumoricidal activity triggered in BMM phagocytes by IFN-gamma or CP, were compared. In concentrations secreted by macrophages under physiological conditions, these agents proved potent in modulating induction and/or expression of tumoricidal activity. However, their ability to interfere with tumoricidal activity varied considerably, depending on the extent of macrophage differentiation and/or functional responsiveness, the pathway of macrophage activation, the type, concentration and combination of the macrophage secretory molecules, and on whether the agents were present during induction and expression or only during expression of tumoricidal activity. In showing that IFN-beta and TNF-alpha were mostly enhancing and TGF-beta mostly suppressive, whereas PGE2 suppressed induction but enhanced expression of tumoricidal activity, our findings provide further support for the concept that these macrophage-derived molecules have a key role in autocrine regulation of macrophage functional activities.