Interleukin-1beta but not IL-1alpha binds to fibrinogen and fibrin and has enhanced activity in the bound form.
Interleukin-1beta but not IL-1alpha binds to fibrinogen and fibrin and has enhanced activity in the bound form.
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发表时间：
2004
期刊：
影响因子：
20.3
通讯作者：
Abha Sahni;M. Guo;S. Sahni;C. Francis
中科院分区：
文献类型：
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作者：
Abha Sahni;M. Guo;S. Sahni;C. Francis
纤维蛋白在损伤或炎症部位形成，并提供临时基质来支持血管细胞反应，而血管细胞反应也是由包括白介素1(IL-1)在内的细胞因子介导的。我们以前已经证明成纤维细胞生长因子2(成纤维细胞生长因子2)与纤维蛋白原有很高的亲和力。由于IL-1具有与成纤维细胞生长因子-2相似的结构，我们研究了IL-1与纤维蛋白原的可能结合。将IL-1固定在琼脂糖珠上，用可溶性碘125(125I)标记纤维蛋白原，结果表明IL-1α与纤维蛋白原无特异性相互作用，而IL-1β呈饱和和特异性结合。Scatchard分析表明结合部位单一，表观K(D)=1.5 nM，IL-1β与纤维蛋白原的最大摩尔结合比为1.8：1。~(125)I-IL-1β与Sephose固定化纤维蛋白原的结合也显示为单一结合部位，表观K(D)为3.5 nM。IL-1β还与纤维蛋白单体和聚合纤维蛋白特异结合，表观K(D)S分别为3.4nM和2.3nM。IL-1β取代了成纤维细胞生长因子-2与纤维蛋白的结合，表明与相同或密切相关的部位相互作用。与游离形式相比，纤维蛋白原结合的IL-1β刺激内皮细胞核因子-kappaB(NF-kappaB)的活化、单核细胞趋化蛋白-1(MCP-1)的分泌和一氧化氮(NO)的合成。我们得出结论，IL-1β与纤维蛋白原具有高亲和力，并以结合的形式显示出更高的活性。
Fibrin is formed at sites of injury or inflammation and provides the temporary matrix to support vascular cell responses that are also mediated by cytokines including interleukin-1 (IL-1). We have shown previously that fibroblast growth factor 2 (FGF-2) binds with high affinity to fibrin(ogen). Because IL-1 has a structure similar to FGF-2, we have investigated the possible binding of IL-1 to fibrin(ogen). Experiments using IL-1 immobilized on Sepharose beads and soluble iodine 125 ((125)I)-labeled fibrinogen demonstrated no specific interaction of IL-1alpha with fibrinogen, but IL-1beta showed saturable and specific binding. Scatchard analysis indicated a single binding site with an apparent K(d) = 1.5 nM and a maximum molar binding ratio of IL-1beta to fibrinogen of 1.8:1. Binding of (125)I-IL-1beta to Sepharose-immobilized fibrinogen also demonstrated a single binding site with an apparent K(d) of 3.5 nM. IL-1beta also bound specifically to fibrin monomer and polymerized fibrin with apparent K(d)s of 3.4 nM and 2.3 nM, respectively. IL-1beta displaced FGF-2 for binding to fibrin, indicating an interaction with the same or a closely related site. Compared with free form, fibrinogen-bound IL-1beta stimulated increased activation of endothelial cell nuclear factor kappaB (NF-kappaB), monocyte chemoattractant protein-1 (MCP-1) secretion, and nitric oxide (NO) synthesis. We conclude that IL-1beta binds with high affinity to fibrin(ogen) and demonstrates increased activity in the bound form.