Goodman M G, Cherry D M
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Cell Immunol. 1989 Oct 15;123(2):417-26. doi: 10.1016/0008-8749(89)90301-8.
The mechanism of action of a group of synthetic lymphokine-like molecules, the C8-substituted guanine ribonucleosides, was studied. Among their pleiotropic effects on B cells are the increased expression of surface Ia antigens, induction of polyclonal immunoglobulin secretion, enhancement of thymus-dependent as well as thymus-independent antibody responses, and transmission of T cell-like differentiative signals to B cells. However, relatively little is known about their molecular mechanism of action. In the current article, the interaction of 8-bromo-guanosine (8BrGuo), a prototypical C8-substituted guanine ribonucleoside, with cellular components was examined. Rapidly exchangeable (free) and slowly exchangeable (bound) 8BrGuo pools exist within B cells. The bound nucleoside pool loses its ability to be retained by a boronate affinity resin (despite its resistance to metabolic processing) and localizes to the cytosol on sucrose density gradients. Binding affinity, ligand specificity, and cellular specificity of binding all correlate closely with observed functional properties of these molecules. Together, these data suggest that the binding interaction mediates the biologic activities of 8BrGuo, and that the binding site acts as a functional nucleoside receptor.
对一组合成的淋巴因子样分子，即C8取代的鸟嘌呤核糖核苷的作用机制进行了研究。它们对B细胞具有多效性作用，包括表面Ia抗原表达增加、诱导多克隆免疫球蛋白分泌、增强胸腺依赖性和非胸腺依赖性抗体反应，以及向B细胞传递T细胞样分化信号。然而，关于它们的分子作用机制了解相对较少。在本文中，研究了典型的C8取代鸟嘌呤核糖核苷8-溴鸟苷（8BrGuo）与细胞成分的相互作用。B细胞内存在快速可交换（游离）和缓慢可交换（结合）的8BrGuo池。结合的核苷池失去了被硼酸亲和树脂保留的能力（尽管其对代谢加工具有抗性），并在蔗糖密度梯度上定位于细胞质溶胶。结合亲和力、配体特异性和结合的细胞特异性都与这些分子观察到的功能特性密切相关。总之，这些数据表明结合相互作用介导了8BrGuo的生物学活性，并且结合位点充当功能性核苷受体。
