Silver nanoparticles and silver ions cause inflammatory response through induction of cell necrosis and the release of mitochondria in vivo and in vitro

Cell Biol Toxicol. 2021 Apr;37(2):177-191. doi: 10.1007/s10565-020-09526-4. Epub 2020 May 4.

Abstract

Owing to the excellent antibacterial and antiviral activity, silver nanoparticles have a widespread use in the food and pharmaceutical industries. With the increase in the production and use of the related products, the potential hazard of silver nanoparticles has aroused public attention. The main purpose of this study is to explore the toxicity of silver nanoparticles and induction of lung inflammation in vitro and in vivo. Here, we validated that small amounts of silver ions dissolved from silver nanoparticles caused the depolarization of plasma membrane, resulting in an overload of intracellular sodium and calcium, and eventually led to the cell necrosis. The blockers of calcium or sodium channels inversed the toxicity of silver ions. Then, we instilled silver nanoparticles or silver nitrate (50 μg per mouse) into the lungs of mice, and this induced pulmonary injury and mitochondrial content release, led to the recruitment of neutrophils to the lung tissue via p38 MAPK pathway. Altogether, these data show that released silver ions from nanoparticles induced cell necrosis through Na+ and Ca2+ influx and triggered pulmonary inflammation through elevating mitochondrial-related contents released from these necrotic cells.

Keywords: Necrosis; Pulmonary inflammation; Silver ions; Silver nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Calcium / metabolism
  • DNA, Mitochondrial / metabolism
  • GTPase-Activating Proteins / metabolism
  • Humans
  • Ions
  • Metal Nanoparticles / adverse effects*
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Necroptosis / drug effects
  • Necrosis
  • Neutrophil Infiltration / drug effects
  • Pneumonia / pathology*
  • Protein Kinases / metabolism
  • Silver / adverse effects*
  • Sodium / metabolism

Substances

  • DNA, Mitochondrial
  • GTPase-Activating Proteins
  • Ions
  • Ralbp1 protein, mouse
  • Silver
  • N-Formylmethionine Leucyl-Phenylalanine
  • Sodium
  • MLKL protein, mouse
  • Protein Kinases
  • Calcium