Balint E, Cheng M, Rupp B, Grimley P M, Aszalos A
Division of Research and Testing, Food and Drug Administration, Washington, DC 20204.
J Interferon Res. 1992 Aug;12(4):249-55. doi: 10.1089/jir.1992.12.249.
Cytochalasin B, a drug that alters microfilament structure, was found to modulate interferon-alpha (IFN-alpha)-induced changes in ion fluxes, in motional freedom of spin probes, and lateral diffusion of surface antigens. These changes occur in Daudi cells inherently sensitive to the antiproliferative signal of IFN-alpha, but not in insensitive cells, and were associated with the antiproliferative signal previously. The biophysical effects of cytochalasin B were detected by flow cytometric quantitation of membrane potential using an oxonol dye, by electron spin resonance (ESR) spectrometry, and by measurements of fluorescence recovery after photobleaching (FRAP) of surface antigens using a laser-interactive cell imaging system. Cytochalasin B treatment increased an IFN-alpha-induced membrane potential shift by -5 mV. The motional freedom of 5-doxyl-stearic acid changed from 0.67 to 0.63, as expressed by the order parameter, S, with IFN-alpha treatment and was prevented by cytochalasin B. Changes in the lateral diffusion of surface antigens induced by IFN-alpha treatment, D = 5.3 x 10(-10) without treatment and D = 7.8 x 10(-10) cm2/s with treatment, was blocked by cytochalasin B. In contrast, the microtubule stabilizers taxol and D2O and the microtubule depolymerizing colcemid were ineffective at dose levels sufficient to cause the characteristic cell physiological alterations of these agents. These results implicate microfilaments but not the microtubule system in transduction of the antiproliferative signal by IFN-alpha in Daudi cells.
细胞松弛素B是一种能改变微丝结构的药物，研究发现它可调节α干扰素（IFN-α）诱导的离子通量变化、自旋探针的运动自由度以及表面抗原的侧向扩散。这些变化发生在对IFN-α抗增殖信号天然敏感的Daudi细胞中，而在不敏感细胞中则不会发生，并且之前已被证明与抗增殖信号相关。通过使用恶嗪醇染料进行流式细胞术定量检测膜电位、通过电子自旋共振（ESR）光谱法以及使用激光交互式细胞成像系统测量表面抗原光漂白后的荧光恢复（FRAP）来检测细胞松弛素B的生物物理效应。细胞松弛素B处理使IFN-α诱导的膜电位偏移增加了-5 mV。5-脱氧硬脂酸的运动自由度在用IFN-α处理后，用序参数S表示从0.67变为0.63，而细胞松弛素B可阻止这种变化。IFN-α处理诱导的表面抗原侧向扩散变化，未处理时D = 5.3×10⁻¹⁰，处理后D = 7.8×10⁻¹⁰ cm²/s，可被细胞松弛素B阻断。相比之下，微管稳定剂紫杉醇和重水以及微管解聚剂秋水仙酰胺在足以引起这些药物特征性细胞生理改变的剂量水平下无效。这些结果表明，在Daudi细胞中，微丝而非微管系统参与了IFN-α抗增殖信号的转导。
