Carbon nanotube recognition by human Siglec-14 provokes inflammation
Carbon nanotube recognition by human Siglec-14 provokes inflammation
复制标题
人类 Siglec-14 识别碳纳米管会引发炎症
DOI：
10.1038/s41565-023-01363-w
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
and Nakayama M
中科院分区：
文献类型：
--
作者：
Yamaguchi S-I;Xie Q,Ito F;Terao K;Kato Y;Kuroiwa M;Omori S;Taniura H;Kinoshita K;Takahashi T;Toyokuni S;Kasahara;K;and Nakayama M
为了设计和开发基于碳纳米管(CNT)的创新工具和应用，了解碳纳米管与生物系统之间的分子相互作用是至关重要的。在这项研究中，基于三维蛋白质结构的电子筛选确定了成对的免疫受体，唾液酸免疫球蛋白样结合凝集素-5(Siglec-5)和Siglec-14，为CNT识别受体。分子动力学模拟表明，Siglec-5胞外环上的芳香族残基与碳纳米管具有稳定的时空结合。Siglec-14介导依赖于脾酪氨酸激酶(Syk)的多壁碳纳米管的吞噬作用以及随后人单核细胞分泌IL-1β。人Siglec-14在小鼠肺泡巨噬细胞上的异位表达导致对多壁碳纳米管的识别增强，并加剧了肺部炎症。此外，Syk抑制剂福斯塔替尼可阻断Siglec-14介导的促炎反应。这些结果表明，Siglec-14是一种识别CNT的人激活受体，阻断Siglec-14和Syk通路可能会克服CNT诱导的炎症。
For the design and development of innovative carbon nanotube (CNT)-based tools and applications, an understanding of the molecular interactions between CNTs and biological systems is essential. In this study, a three-dimensional protein-structure-based in silico screen identified the paired immune receptors, sialic acid immunoglobulin-like binding lectin-5 (Siglec-5) and Siglec-14, as CNT-recognizing receptors. Molecular dynamics simulations showed the spatiotemporally stable association of aromatic residues on the extracellular loop of Siglec-5 with CNTs. Siglec-14 mediated spleen tyrosine kinase (Syk)-dependent phagocytosis of multiwalled CNTs and the subsequent secretion of interleukin-1β from human monocytes. Ectopic in vivo expression of human Siglec-14 on mouse alveolar macrophages resulted in enhanced recognition of multiwalled CNTs and exacerbated pulmonary inflammation. Furthermore, fostamatinib, a Syk inhibitor, blocked Siglec-14-mediated proinflammatory responses. These results indicate that Siglec-14 is a human activating receptor recognizing CNTs and that blockade of Siglec-14 and the Syk pathway may overcome CNT-induced inflammation.
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影响因子：
38.3
作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
5.8
作者：
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通讯作者：
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影响因子：
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Velankar S
基于误解的 SIN 名单批评
影响因子：
38.3
作者：
S. Hansen;Anna Lennquist
通讯作者：
Anna Lennquist