한빛사논문
Dong-Keun Lee1†, Gyuri Kim1†, Muthuchamy Maruthupandy1, Kyuhong Lee2 and Wan-Seob Cho1*
1Lab of Toxicology, Department of Health Sciences, Dong-A University, 37, Nakdong-daero 550 beon-gil, Saha-gu, Busan 49315, Republic of Korea
2Inhalation Toxicology Center for Airborne Risk Factor, Korea Institute of Toxicology, 30 Baehak1-gil, Jeongeup 56212, Jeollabuk-do, Republic of Korea
†Dong-Keun Lee and Gyuri Kim contributed equally to this work.
*Correspondence: Wan-Seob Cho
Abstract
Background: 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.
Results: 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.
Conclusions: 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.
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