Anti-inflammatory activity of low molecular weight polysialic acid on human macrophages.
Anti-inflammatory activity of low molecular weight polysialic acid on human macrophages.
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DOI：
10.1038/srep16800
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发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
Neumann H
中科院分区：
文献类型：
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作者：
Shahraz A;Kopatz J;Mathy R;Kappler J;Winter D;Kapoor S;Schütza V;Scheper T;Gieselmann V;Neumann H
神经细胞和免疫细胞糖萼的寡聚唾液酸和聚唾液酸（oligoSia和polySia）是线性链，其中唾液酸单体是α2.8-糖苷连接的。唾液酸结合免疫球蛋白样凝集素-11 （SIGLEC-11）是人类组织巨噬细胞和小胶质细胞的灵长类谱系特异性受体，可结合α2.8-linked oligoSia。在这里，我们发现平均聚合度为20的可溶性低分子量聚sia （avDP20）与SIGLEC-11相互作用，并对涉及SIGLEC-11受体的人THP1巨噬细胞起抗炎作用。可溶性聚sia avDP20抑制脂多糖（LPS）诱导的肿瘤坏死因子-α (tumor necrosis factor Superfamily Member 2, TNFSF2)基因转录和蛋白表达。此外，polySia avDP20可以中和lps引发的巨噬细胞吞噬增加，但不影响基础吞噬和内吞作用。此外，多sia avDP20可阻止神经碎片或原纤维淀粉样蛋白-β1-42引发的人巨噬细胞氧化破裂。在人巨噬细胞-神经元共培养系统中，polySia avDP20也减少了由原纤维淀粉样蛋白-β1-42引发的神经突损失。因此，用polySia avDP20治疗可能是一种新的抗炎治疗策略，也可以防止巨噬细胞的氧化爆发。
Oligosialic and polysialic acid (oligoSia and polySia) of the glycocalyx of neural and immune cells are linear chains, in which the sialic acid monomers are α2.8-glycosidically linked. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a primate-lineage specific receptor of human tissue macrophages and microglia that binds to α2.8-linked oligoSia. Here, we show that soluble low molecular weight polySia with an average degree of polymerization 20 (avDP20) interacts with SIGLEC-11 and acts anti-inflammatory on human THP1 macrophages involving the SIGLEC-11 receptor. Soluble polySia avDP20 inhibited the lipopolysaccharide (LPS)-induced gene transcription and protein expression of tumor necrosis factor-α (Tumor Necrosis Factor Superfamily Member 2, TNFSF2). In addition, polySia avDP20 neutralized the LPS-triggered increase in macrophage phagocytosis, but did not affect basal phagocytosis or endocytosis. Moreover, polySia avDP20 prevented the oxidative burst of human macrophages triggered by neural debris or fibrillary amyloid-β1–42. In a human macrophage-neuron co-culture system, polySia avDP20 also reduced loss of neurites triggered by fibrillary amyloid-β1–42. Thus, treatment with polySia avDP20 might be a new anti-inflammatory therapeutic strategy that also prevents the oxidative burst of macrophages.