Chemokine receptor 4 (CXCR4) is part of the lipopolysaccharide "sensing apparatus"

Chemokine receptor 4 (CXCR4) is part of the lipopolysaccharide "sensing apparatus"
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DOI:
10.1002/eji.200636821
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发表时间:
2008-01-01
影响因子:
5.4
通讯作者:
Triantafilou, Kathy
Triantafilou, Kathy
中科院分区:
医学3区
文献类型:
--
作者:
Triantafilou, Martha;Lepper, Philipp M.;Triantafilou, Kathy

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先天免疫系统对细菌脂多糖(LPS)的识别涉及至少三种受体分子:CD 14、TLR 4和MD-2。其他受体成分,例如热休克蛋白、趋化因子受体4(CXCR 4)或CD 55已被认为是该激活簇的一部分;可能充当其他LPS转移分子。我们的小组先前已经确定CXCR 4是“LPS传感装置”的一个组成部分。在这项研究中,我们的目的是阐明CXCR 4在先天免疫反应中发挥的作用,LPS。在这里,我们证明了CXCR 4转染导致对LPS的反应性。荧光相关光谱实验进一步表明LPS直接与CXCR 4相互作用。我们的数据表明,CXCR 4不仅参与LPS结合,但也负责触发信号,特别是丝裂原活化蛋白激酶在响应LPS。最后,CXCR 4与其他LPS受体的共聚集似乎对LPS信号传导至关重要,因此表明CXCR 4是多聚体LPS“传感装置”的功能部分。
Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system involves at least three receptor molecules: CD14, TLR4 and MD-2. Additional receptor components such as heat shock proteins, chemokine receptor 4 (CXCR4), or CD55 have been suggested to be part of this activation cluster; possibly acting as additional LPS transfer molecules. Our group has previously identified CXCR4 as a component of the "LPS-sensing apparatus". In this study we aimed to elucidate the role that CXCR4 plays in innate immune responses to LPS. Here we demonstrate that CXCR4 transfection results in responsiveness to LPS. Fluorescence correlation spectroscopy experiments further showed that LPS directly interacts with CXCR4. Our data suggest that CXCR4 is not only involved in LPS binding but is also responsible for triggering signalling, especially mitogen-activated protein kinases in response to LPS. Finally, co-clustering of CXCR4 with other LPS receptors seems to be crucial for LPS signalling, thus suggesting that CXCR4 is a functional part of the multimeric LPS "sensing apparatus".