Time-resolved characterization of the mechanisms of toxicity induced by silica and amino-modified polystyrene on alveolar-like macrophages

Sarah Deville, Birgit Honrath, Quynh T D Tran, Gyorgy Fejer, Ivo Lambrichts, Inge Nelissen, Amalia M Dolga, Anna Salvati*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

Macrophages play a major role in the removal of foreign materials, including nano-sized materials, such as nanomedicines and other nanoparticles, which they accumulate very efficiently. Because of this, it is recognized that for a safe development of nanotechnologies and nanomedicine, it is essential to investigate potential effects induced by nano-sized materials on macrophages. To this aim, in this work, a recently established model of primary murine alveolar-like macrophages was used to investigate macrophage responses to two well-known nanoparticle models: 50 nm amino-modified polystyrene, known to induce cell death via lysosomal damage and apoptosis in different cell types, and 50 nm silica nanoparticles, which are generally considered non-toxic. Then, a time-resolved study was performed to characterize in detail the response of the macrophages following exposure to the two nanoparticles. As expected, exposure to the amino-modified polystyrene led to cell death, but surprisingly no lysosomal swelling or apoptosis were detected. On the contrary, a peculiar mitochondrial membrane hyperpolarization was observed, accompanied by endoplasmic reticulum stress (ER stress), increased cellular reactive oxygen species (ROS) and changes of metabolic activity, ultimately leading to cell death. Strong toxic responses were observed also after exposure to silica, which included mitochondrial ROS production, mitochondrial depolarization and cell death by apoptosis. Overall, these results showed that exposure to the two nanoparticles led to a very different series of intracellular events, suggesting that the macrophages responded differently to the two nanoparticle models. Similar time-resolved studies are required to characterize the response of macrophages to nanoparticles, as a key parameter in nanosafety assessment.

Original languageEnglish
Pages (from-to)173-186
Number of pages14
JournalArchives of toxicology
Volume94
Issue number1
Early online date1-Nov-2019
DOIs
Publication statusPublished - 2020

Keywords

  • IRON-OXIDE NANOPARTICLES
  • CELL-DEATH
  • NANOMATERIALS
  • MITOCHONDRIA
  • PHARMACOKINETICS
  • NANOTECHNOLOGY
  • OPPORTUNITIES
  • NANOMEDICINE
  • PARTICLES
  • AUTOPHAGY

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