Polysialic acid interacts with lactoferrin and supports its activity to inhibit the release of neutrophil extracellular traps
Polysialic acid interacts with lactoferrin and supports its activity to inhibit the release of neutrophil extracellular traps
复制标题
DOI：
10.1016/j.carbpol.2018.12.033
复制
发表时间：
2019-03-15
影响因子：
11.2
通讯作者：
Galuska, Sebastian P.
中科院分区：
文献类型：
--
作者：
Kuehnle, Andrea;Veelken, Rhea;Galuska, Sebastian P.
聚唾液酸（polySia）是一种线性碳水化合物聚合物，由N-乙酰神经氨酸残基组成，参与多种生理过程。在本研究中，我们确定了多功能蛋白质乳铁蛋白作为一种新的相互作用的合作伙伴polySia。当从人血液、乳汁和精液样品中分离polySia时，乳铁蛋白共沉淀。使用天然凝胶电泳应用验证了polySia和乳铁蛋白之间的相互作用，表明这种相互作用取决于聚合度。分子之间的相互作用可以通过针对乳铁蛋白的抗体（LFcin）来抑制，这表明乳铁蛋白的LFcin结构域代表唾液酸聚合物的潜在结合区域。由于乳铁蛋白抑制中性粒细胞胞外陷阱（NET）的形成，因此测试了polySia对乳铁蛋白的该功能的潜在影响。有趣的是，我们观察到polySia提高了乳铁蛋白的效率，以防止NET纤维的释放。单独的PolySia没有显示出活性。因此，与乳铁蛋白一起，polySia可能代表NET释放的天然调节系统。
Polysialic acid (polySia) is a linear carbohydrate polymer consisting of N-acetylneuraminic acid residues and is involved in several physiological processes. In the present study, we identified the multifunctional protein lactoferrin as a novel interaction partner for polySia. Lactoferrin co-precipitated when polySia was isolated from human blood, milk, and semen samples. The interaction between polySia and lactoferrin was verified using a native gel electrophoresis application, demonstrating that such interaction depends on the degree of polymerization. The interaction between the molecules could be inhibited by an antibody against lactoferricin (LFcin), which suggests that the LFcin domain of lactoferrin represents the potential binding area for sialic acid polymers. Because lactoferrin inhibits the formation of neutrophil extracellular traps (NETs), the potential impact of polySia on this function of lactoferrin was tested. Intriguingly, we observed that polySia increases the efficiency of lactoferrin to prevent the release of NET fibers. PolySia alone shows no activity. Therefore, together with lactoferrin, polySia may represent a natural regulatory system of NET release.