Multiple pathways of alveolar macrophage death contribute to pulmonary inflammation induced by silica nanoparticles

Eun Jung Park, Min Sung Kang, Seung Woo Jin, Tae Geol Lee, Gwang Hee Lee, Dong Wan Kim, Eun Woo Lee, Junhee Park, Inhee Choi, Youngmi Kim Pak

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


In our previous study, 20 nm-sized amorphous silica nanoparticles (20-SiNPs), but not 50 nm-sized amorphous silica nanoparticles (50-SiNPs), induced pulmonary inflammatory response in rats exposed repeatedly for 14 days (12.5, 25, and 50 μg/time, total six times). In this study, we tried to clarify the causes of different responses induced by both SiNPs using mice (12.5, 25, and 50 μg/lung) and mouse alveolar macrophage cells. When exposed to alveolar macrophage cells for 24 h, both SiNPs decreased cell viability and enhanced ROS generation compared to controls. The 20- and 50-SiNPs also formed giant and autophagosome-like vacuoles in the cytoplasm, respectively. Structural damage of organelles was more pronounced in 20-SiNPs-treated cells than in 50-SiNPs-treated cells, and an increased mitochondrial membrane potential and mitochondrial calcium accumulation were observed only in the 20-SiNPs-treated cells. Additionally, a single intratracheal instillation of both sizes of SiNPs to mice clearly elevated the relative proportion of neutrophils and inhibited differentiation of macrophages and expression of an adhesion molecule. Meanwhile, interestingly, the total number of pulmonary cells and the levels of pro-inflammatory mediators more notably increased in the lungs of mice exposed to 20-SiNPs compared to 50-SiNPs. Given that accumulation of giant vacuoles and dilation of the ER and mitochondria are key indicators of paraptosis, we suggest that 20-SiNPs-induced pulmonary inflammation may be associated with paraptosis of alveolar macrophages.

Original languageEnglish
Pages (from-to)1087-1101
Number of pages15
Issue number8
StatePublished - 2021


  • Silica nanoparticles
  • endoplasmic reticulum
  • inflammation
  • paraptosis
  • size
  • vacuoles


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