Poltorak A, Ricciardi-Castagnoli P, Citterio S, Beutler B
The Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2163-7. doi: 10.1073/pnas.040565397.
Some mammalian species show an ability to discriminate between different lipopolysaccharide (LPS) partial structures (for example, lipid A and its congener LA-14-PP, which lacks secondary acyl chains), whereas others do not. Using a novel genetic complementation system involving the transduction of immortalized macrophages from genetically unresponsive C3H/HeJ mice, we now have shown that the species-dependent discrimination between intact LPS and tetra-acyl LPS partial structures is fully attributable to the species origin of Toll-like receptor 4 (Tlr4), an essential membrane-spanning component of the mammalian LPS sensor. Because Tlr4 interprets the chemical structure of an LPS molecule, we conclude that LPS must achieve close physical proximity with Tlr4 in the course of signal transduction.
一些哺乳动物物种表现出能够区分不同的脂多糖(LPS)部分结构(例如,脂质A及其同系物LA-14-PP,后者缺乏二级酰基链),而其他物种则不能。利用一种新型的基因互补系统,该系统涉及从基因无反应的C3H/HeJ小鼠中转导永生化巨噬细胞,我们现在已经表明,完整LPS和四酰基LPS部分结构之间的物种依赖性区分完全归因于Toll样受体4(Tlr4)的物种起源,Tlr4是哺乳动物LPS传感器的一种必需的跨膜成分。由于Tlr4解读LPS分子的化学结构,我们得出结论,LPS在信号转导过程中必须与Tlr4实现紧密的物理接近。