Aszalos A, Grimley P M, Balint E, Chadha K C, Ambrus J L
Division of Research and Testing, FDA, Washington, DC.
J Med. 1991;22(4-5):255-71.
In earlier studies, we showed that when interferon alpha (IFN alpha) binds to cell receptors, it alters membrane potentials. In IFN-sensitive Daudi cells derived from Burkitt's lymphoma patients, IFNs produce dose-dependent hyperpolarization, decreased plasma membrane viscosity, modulation of the microfilament system, and altered synthesis of cAMP, cGMP and prostaglandins. No such changes were seen in IFN alpha-resistant Daudi cells. In this study, we found that indomethacin, pentoxifylline, or the cGMP inducer sodium azide (NaN3) had no significant effect on the IFN alpha induced membrane potential changes, or on membrane viscosity changes as measured by flow cytometry and electron spin resonance spectrometry. In tissue culture, indomethacin did not alter the anti-proliferative effect of IFN alpha on Daudi cells. Indomethacin may influence IFN synthesis, but not it's antiproliferative actions. Relatively high doses of pentoxifylline slightly inhibited proliferation of Daudi cells and synergized with IFN alpha. Measurement of early biophysical changes induced by IFNs may represent a new screening method to rapidly explore certain types of IFN alpha potentiating agents.
在早期研究中，我们发现当干扰素α（IFNα）与细胞受体结合时，会改变膜电位。在源自伯基特淋巴瘤患者的对IFN敏感的Daudi细胞中，IFN会产生剂量依赖性超极化、降低质膜粘度、调节微丝系统，并改变cAMP、cGMP和前列腺素的合成。在对IFNα耐药的Daudi细胞中未观察到此类变化。在本研究中，我们发现吲哚美辛、己酮可可碱或cGMP诱导剂叠氮化钠（NaN3）对IFNα诱导的膜电位变化或通过流式细胞术和电子自旋共振光谱法测量的膜粘度变化没有显著影响。在组织培养中，吲哚美辛不会改变IFNα对Daudi细胞的抗增殖作用。吲哚美辛可能会影响IFN的合成，但不会影响其抗增殖作用。相对高剂量的己酮可可碱会轻微抑制Daudi细胞的增殖，并与IFNα协同作用。测量IFN诱导的早期生物物理变化可能代表一种新的筛选方法，用于快速探索某些类型的IFNα增强剂。
