Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M
Department of Immunology, Saga Medical School, Saga, Japan.
J Exp Med. 1999 Jun 7;189(11):1777-82. doi: 10.1084/jem.189.11.1777.
Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.
Toll样受体4（TLR4）是果蝇Toll的哺乳动物同源物，Toll是一种富含亮氨酸的重复分子，可触发针对病原体的先天性免疫反应。最近发现，在对脂多糖（LPS）反应较弱的C3H/HeJ和C57BL/10ScCr小鼠中，TLR4基因发生了突变。TLR4可能是人们长期寻找的LPS受体。然而，将TLR4转染到受体细胞系中并不能使其对LPS产生反应，这表明还需要另外一种分子。在此，我们报告一种新分子MD-2是TLR4的LPS信号传导所必需的。MD-2在细胞表面与TLR4物理结合，并赋予细胞对LPS的反应能力。因此，MD-2是TLR4与LPS信号传导之间的连接分子。这一新受体复合物的鉴定对于理解宿主防御以及病理生理机制具有潜在意义。
