PDF(Pubmed)
Abstract：
Alveolar macrophages (AMs) have been predicted to affect the pulmonary clearance of nanomaterials; however, their qualitative and quantitative roles are poorly understood. In this study, carbon black nanoparticles (CBNPs) were instilled into the lungs of Wistar rats at 30, 100, and 300 µg/rat. The concentrations of particles in organs, including the lung, lung-associated lymph nodes (LALN), liver, spleen, and kidney, were evaluated at days 0 (immediately after instillation), 1, 7, 28, 60, and 90 post-instillation.
The results indicated a multimodal pulmonary clearance pattern for CBNPs: slow clearance until day 28, fast clearance from days 28 to 60, and slow clearance from days 60 to 90. To determine the mechanism of this unique clearance pattern, CBNPs were instilled into AM-depleted rats using clodronate liposomes (CLO). At 28 days after instillation, the CBNP levels in the lungs treated with CLO showed about 31% higher reduction than in normal rats. In addition, the concentration of CBNPs in LALN treated with CLO significantly increased on day 28, whereas in normal rats, no detectable levels were observed.
This result highlights that the prolonged retention of poorly soluble NPs in the lung until day 28 is mediated by the phagocytosis of AMs, and the fast clearance between days 28-60 is due to the turnover time of AMs, estimated around 1-2 months after birth. Similarly, new generations of AMs mediate the slow phase between days 60 and 90. However, further studies are needed to understand the multimodal clearance mechanism and the modulation of pulmonary clearance of poorly soluble NPs.
The results indicated a multimodal pulmonary clearance pattern for CBNPs: slow clearance until day 28, fast clearance from days 28 to 60, and slow clearance from days 60 to 90. To determine the mechanism of this unique clearance pattern, CBNPs were instilled into AM-depleted rats using clodronate liposomes (CLO). At 28 days after instillation, the CBNP levels in the lungs treated with CLO showed about 31% higher reduction than in normal rats. In addition, the concentration of CBNPs in LALN treated with CLO significantly increased on day 28, whereas in normal rats, no detectable levels were observed.
This result highlights that the prolonged retention of poorly soluble NPs in the lung until day 28 is mediated by the phagocytosis of AMs, and the fast clearance between days 28-60 is due to the turnover time of AMs, estimated around 1-2 months after birth. Similarly, new generations of AMs mediate the slow phase between days 60 and 90. However, further studies are needed to understand the multimodal clearance mechanism and the modulation of pulmonary clearance of poorly soluble NPs.
摘要：
背景：已预测肺泡巨噬细胞（AMs）会影响纳米材料的肺清除；然而，他们的定性和定量作用知之甚少。在这项研究中,将炭黑纳米颗粒（CBNPs）以30、100和300µg/大鼠的剂量滴入Wistar大鼠的肺中。器官中颗粒的浓度，包括肺,肺相关淋巴结（LALN），肝脏,脾,脾和肾脏，在第0天（滴注后立即）进行评估，1、7、28、60和90后滴注。
结果：结果表明CBNP的多模式肺清除模式：缓慢清除至第28天，快速清除至第28天，缓慢清除至第60天，缓慢清除至第60天。为了确定这种独特的间隙模式的机制，使用氯膦酸盐脂质体（CLO）将CBNP滴入AM耗尽的大鼠中。滴注后28天，用CLO处理的肺中的CBNP水平显示比正常大鼠高约31%的降低。此外,在第28天用CLO处理的LALN中CBNPs的浓度显著增加,而在正常大鼠中,没有观察到可检测的水平。
结论：该结果突出表明，在第28天之前，难溶性NPs在肺中的长时间保留是由AMs的吞噬作用介导的，28-60天之间的快速清仓是由于AM的周转时间，出生后大约1-2个月。同样，新一代AMs在第60天至90天之间介导缓慢阶段。然而,需要进一步的研究来了解多峰清除机制和低可溶性NPs的肺清除的调节。
结果：结果表明CBNP的多模式肺清除模式：缓慢清除至第28天，快速清除至第28天，缓慢清除至第60天，缓慢清除至第60天。为了确定这种独特的间隙模式的机制，使用氯膦酸盐脂质体（CLO）将CBNP滴入AM耗尽的大鼠中。滴注后28天，用CLO处理的肺中的CBNP水平显示比正常大鼠高约31%的降低。此外,在第28天用CLO处理的LALN中CBNPs的浓度显著增加,而在正常大鼠中,没有观察到可检测的水平。
结论：该结果突出表明，在第28天之前，难溶性NPs在肺中的长时间保留是由AMs的吞噬作用介导的，28-60天之间的快速清仓是由于AM的周转时间，出生后大约1-2个月。同样，新一代AMs在第60天至90天之间介导缓慢阶段。然而,需要进一步的研究来了解多峰清除机制和低可溶性NPs的肺清除的调节。
