The objective of this study was to examine the threshold fibre length for the onset of pulmonary inflammation after aspiration exposure in mice to four different lengths of silver nanowires (AgNW). We further examined the effect of fibre length on macrophage locomotion in an in vitro wound healing assay. We hypothesised that exposure to longer fibres causes both increased inflammation and restricted mobility leading to impaired clearance of long fibres from the lower respiratory tract to the mucociliary escalator in vivo. Nine week old female C57BL/6 strain mice were exposed to AgNW and controls via pharyngeal aspiration. The dose used in this study was equalised to fibre number and based on 50 μg/ mouse for AgNW14. To examine macrophage migration in vitro a wound healing assay was used. An artificial wound was created in a confluent layer of bone marrow derived macrophages by scraping with a pipette tip and the number of cells migrating into the wound was monitored microscopically. The dose was equalised for fibre number and based on 2.5 μg/cm2 for AgNW14. Aspiration of AgNW resulted in a length dependent inflammatory response in the lungs with threshold at a fibre length of 14 μm. Shorter fibres including 3, 5 and 10 μm elicited no significant inflammation. Macrophage locomotion was also restricted in a length dependent manner whereby AgNW in the length of ≥5 μm resulted in impaired motility in the wound closure assay. We demonstrated a 14 μm cut-off length for fibre-induced pulmonary inflammation after aspiration exposure and an in vitro threshold for inhibition of macrophage locomotion of 5 μm. We previously reported a threshold length of 5 μm for fibre-induced pleural inflammation. This difference in pulmonary and pleural fibre- induced inflammation may be explained by differences in clearance mechanism of deposited fibres from the airspaces compared to the pleural space. Inhibition of macrophage migration at long fibre lengths could account for their well-documented long term retention in the lungs compared to short fibres. Knowledge of the threshold length for acute pulmonary inflammation contributes to hazard identification of nanofibres.

中文翻译：

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使用银纳米线确定纤维长度依赖性肺部炎症的阈值和体外巨噬细胞迁移的抑制。

本研究的目的是检查小鼠吸入暴露于四种不同长度的银纳米线 (AgNW) 后肺部炎症发生的阈值纤维长度。我们在体外伤口愈合试验中进一步研究了纤维长度对巨噬细胞运动的影响。我们假设暴露于较长的纤维会导致炎症增加和活动受限，从而导致体内长纤维从下呼吸道到粘膜纤毛自动扶梯的清除受损。九周大的雌性 C57BL/6 品系小鼠通过咽部抽吸暴露于 AgNW 和对照。本研究中使用的剂量与纤维数量相等，并基于 AgNW14 50 μg/小鼠。为了检查巨噬细胞的体外迁移，使用了伤口愈合测定。通过用移液管尖端刮擦，在源自骨髓的巨噬细胞的汇合层中产生人工伤口，并用显微镜监测迁移到伤口中的细胞数量。纤维数量的剂量是均衡的，AgNW14 的剂量基于 2.5 μg/cm2。AgNW 的吸入导致肺部出现长度依赖性炎症反应，纤维长度的阈值为 14 μm。包括 3、5 和 10 μm 在内的较短纤维不会引起明显的炎症。巨噬细胞的运动也受到长度依赖性的限制，其中长度≥5μm的AgNW导致伤口闭合测定中的运动受损。我们证明了吸入暴露后纤维诱发的肺部炎症的截止长度为 14 μm，抑制巨噬细胞运动的体外阈值为 5 μm。我们之前报道了纤维引起的胸膜炎症的阈值长度为 5 μm。肺部和胸膜纤维引起的炎症的这种差异可以通过与胸膜腔相比从气腔沉积的纤维的清除机制的差异来解释。与短纤维相比，长纤维长度对巨噬细胞迁移的抑制可能是其在肺部长期滞留的原因。了解急性肺部炎症的阈值长度有助于纳米纤维的危险识别。