Elass Elisabeth, Coddeville Bernadette, Guérardel Yann, Kremer Laurent, Maes Emmanuel, Mazurier Joël, Legrand Dominique
Unité Mixte de Recherche n 8576 du Centre National de la Recherche Scientifique, Institut Fédératif de Recherche 147, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
FEBS Lett. 2007 Apr 3;581(7):1383-90. doi: 10.1016/j.febslet.2007.02.056. Epub 2007 Mar 2.
The mycobacterial lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM), regulate host defence mechanisms through their interaction with pattern recognition receptors such as Toll-like receptors (TLRs). We have developed a surface plasmon resonance assay to analyse the molecular basis for the recognition of Mycobacterium kansasii LM or LAM, by immobilized CD14 and LPS-binding protein (LBP) both being capable to promote presentation of bacterial glycolipids to TLRs. The affinity of either LM/LAM was higher to CD14 than to LBP. Kinetic and Scatchard analyses were consistent with a model involving a single class of binding sites. These interactions required the lipidic anchor, but not the carbohydrate domains, of LM or LAM. We also provide evidence that addition of recombinant LBP enhanced the stimulatory effect of LM or LAM on matrix metalloproteinase-9 expression and secretion in macrophages, through a TLR1/TLR2-dependent mechanism.
分枝杆菌脂糖、脂甘露聚糖（LM）和脂阿拉伯甘露聚糖（LAM）通过与Toll样受体（TLR）等模式识别受体相互作用来调节宿主防御机制。我们开发了一种表面等离子体共振分析方法，以分析堪萨斯分枝杆菌LM或LAM被固定化的CD14和脂多糖结合蛋白（LBP）识别的分子基础，这两者都能够促进细菌糖脂向TLR的呈递。LM/LAM与CD14的亲和力高于与LBP的亲和力。动力学和Scatchard分析与涉及单一类结合位点的模型一致。这些相互作用需要LM或LAM的脂质锚定，但不需要其碳水化合物结构域。我们还提供证据表明，添加重组LBP通过TLR1/TLR2依赖性机制增强了LM或LAM对巨噬细胞中基质金属蛋白酶-9表达和分泌的刺激作用。
