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机构地区:[1]第三军医大学大坪医院野战外科研究所第一研究室,重庆400042
出 处:《生理科学进展》2004年第2期139-142,共4页Progress in Physiological Sciences
基 金:国家重点基础研究发展规划项目 (973) (G19990 5 4 2 0 3)资助课题
摘 要:Toll样受体 (Toll likereceptor ,TLR)家族作为模式识别受体 ,在天然免疫中具有重要作用。髓样分化蛋白 2 (myeloiddifferentialprotein 2 ,MD 2 )可能含有两个相对独立的功能结构域 ,既能与Toll样受体家族中的TLR4、TLR2结合 ,也能与多种配体结合 (包括lipopolysaccharide ,LPS)。这种特殊的结构可能与其三方面的主要功能有关 :(1)MD 2与TLR4结合 ,赋予TLR4对各种配体 (包括LPS)的反应性 ;(2 )MD 2与TLR2结合 ,赋予TLR2对LPS的反应性 ,并增强TLR2对细菌及其胞壁成分的反应性 ;(3)MD 2能促进TLR4和TLR2的表达 ,并且与TLR4在细胞内的分布密切相关。这表明MD 2可以通过两种方式直接或间接调控TLRs的功能 :与TLR2 /TLR4结合 ,或调控TLR2 /TLR4的表达与分布。因而MD 2不仅仅是TLR4的辅助分子 ,而且还是天然免疫中的调控分子 ,可能在感染、炎症。As typical PRRs (pattern-recognition receptors), TLRs (Toll-like receptors) play an important role during innate immunity recognition. MD-2 (myeloid differential protein-2) may contain distinct functional domains that can separately and simultaneously bind TLRs (TLR4 or TLR2) and TLR ligands, such as lipopolysaccharide (LPS). The special structure of MD-2 may result in its three main functions:(1) An association with TLR4 that amplifies TLR4 responsiveness to ligands, especially LPS.(2) Enabling TLR2-mediated responses to LPS and enhancing TLR2-mediated responses to bacteria and their cell wall components.(3) Increasing the expression of TLR2 and TLR4 and possibly influencing the correct intracellular distribution of TLR4. Importantly, while MD-2 regulation of TLR expression and distribution is well established, determining whether the interaction is direct or not will require further study. Thus, MD-2 is not only an assistant molecule of TLR4 but is also a key regulatory molecule in innate immunity, and may play important roles during infection, inflammation, immune responses and many other pathologic and physiologic processes.
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