Hogan M M, Vogel S N
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1988 Jan 15;140(2):513-9.
In this study, the effect of corticosteroids on the activation of macrophages to a fully tumoricidal state was examined. Thioglycolate-elicited peritoneal exudate macrophages from C3H/HeJ mice were rendered cytolytic for P815 mastocytoma cells in a two-signal tumoricidal assay that used recombinant interferon-gamma (rIFN-gamma; 1 to 10 U/ml) as a "priming" signal and butanol-extracted lipopolysaccharide (But-LPS; 0.1 to 5 micrograms/ml) as a "trigger" signal. Treatment of macrophages with either rIFN-gamma alone or But-LPS alone failed to result in significant cytolytic ability. Tumoricidal activity was markedly inhibited in a dose-dependent fashion when glucocorticoids were added simultaneously to the cultures with rIFN-gamma and But-LPS at concentrations ranging from 1 X 10(-10) to 1 X 10(-5) M. Nonglucocorticoid sex hormones failed to inhibit tumoricidal activity in this system under identical culture conditions. Inhibition was most effective if the glucocorticoids were added simultaneously with the priming and triggering signals (rIFN-gamma and But-LPS); however, if the glucocorticoids were added 24 hr after the signals were provided to the cultures, suboptimal inhibition was observed. Experiments that dissociated the priming phase of activation from the triggering phase showed that glucocorticoids inhibited both the rIFN-gamma-induced priming stage as well as the But-LPS-induced triggering stage of activation. These observations provide evidence that glucocorticoids, but not other steroid hormones, inhibit the activation of macrophages to a fully tumoricidal state by interfering with either the priming or triggering signals in this two-signal model of macrophage activation.
在本研究中，检测了皮质类固醇对巨噬细胞激活至完全杀肿瘤状态的影响。在一项双信号杀肿瘤试验中，用重组干扰素-γ（rIFN-γ；1至10 U/ml）作为“启动”信号，用丁醇提取的脂多糖（But-LPS；0.1至5 μg/ml）作为“触发”信号，使来自C3H/HeJ小鼠的巯基乙酸盐诱导的腹腔渗出巨噬细胞对P815肥大细胞瘤细胞具有细胞溶解作用。单独用rIFN-γ或单独用But-LPS处理巨噬细胞均未能产生显著的细胞溶解能力。当糖皮质激素与rIFN-γ和But-LPS同时以1×10⁻¹⁰至1×10⁻⁵ M的浓度添加到培养物中时，杀肿瘤活性以剂量依赖性方式显著受到抑制。在相同培养条件下，非糖皮质激素性激素未能抑制该系统中的杀肿瘤活性。如果糖皮质激素与启动和触发信号（rIFN-γ和But-LPS）同时添加，抑制效果最为显著；然而，如果在向培养物提供信号24小时后添加糖皮质激素，则观察到次优抑制。将激活的启动阶段与触发阶段分离的实验表明，糖皮质激素抑制rIFN-γ诱导的启动阶段以及But-LPS诱导的激活触发阶段。这些观察结果提供了证据，表明糖皮质激素而非其他类固醇激素通过干扰巨噬细胞激活的双信号模型中的启动或触发信号，抑制巨噬细胞激活至完全杀肿瘤状态。
