MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4.
MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4.
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DOI：
10.1084/jem.189.11.1777
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发表时间：
1999-06-07
期刊：
影响因子：
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通讯作者：
Kimoto M
中科院分区：
文献类型：
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作者：
Shimazu R;Akashi S;Ogata H;Nagai Y;Fukudome K;Miyake K;Kimoto M
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，可以触发对病原体的先天性反应。最近发现TLR4基因在C3H/HeJ和C57BL/10Sccr小鼠中发生突变，这两种小鼠对脂多糖(LPS)的反应都很低。TLR4可能是一个长期寻找的内毒素受体。然而，TLR4的转导并不能使受体细胞产生内毒素反应，这意味着需要额外的分子。在这里，我们报道了一个新的分子MD-2，它是内毒素信号转导TLR4所必需的。MD-2在物理上与细胞表面的TLR4相关，并赋予其对内毒素的反应性。因此，MD-2是TLR4和内毒素信号之间的链接。这种新的受体复合体的鉴定对于理解寄主防御和病理生理机制具有潜在的意义。
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.