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.

对于基于创新碳纳米管 (CNT) 的工具和应用的设计和开发，了解 CNT 与生物系统之间的分子相互作用至关重要。在这项研究中，基于三维蛋白质结构的计算机屏幕将配对的免疫受体、唾液酸免疫球蛋白样结合凝集素 5 (Siglec-5) 和 Siglec-14 识别为 CNT 识别受体。分子动力学模拟表明，Siglec-5 细胞外环上的芳香族残基与 CNT 在时空上稳定结合。Siglec-14 介导脾脏酪氨酸激酶 (Syk) 依赖性多壁碳纳米管的吞噬作用以及随后从人单核细胞分泌白介素-1β。人 Siglec-14 在小鼠肺泡巨噬细胞上的异位体内表达导致对多壁 CNT 的识别增强并加剧了肺部炎症。此外，Syk 抑制剂 fostamatinib 可阻断 Siglec-14 介导的促炎反应。这些结果表明 Siglec-14 是识别 CNT 的人类激活受体，并且阻断 Siglec-14 和 Syk 通路可以克服 CNT 诱导的炎症。