Charged polyhedral oligomeric silsesquioxanes trigger in vitro METosis via both oxidative stress and autophagy

Stelvio Tonello1, Fabio Carniato2, Manuela Rizzi1

  • 1Health Sciences Department, Università del Piemonte Orientale "A. Avogadro", Via Solaroli, 17, 28100 Novara, Italy.

Life Sciences
|October 3, 2017
PubMed
Abstract

Insights

Polyhedral oligomeric silsesquioxanes (POSS) can induce monocytes/macrophages to release extracellular traps (METs) through oxidative and autophagic pathways, regardless of their charge. This process involves POSS internalization and is crucial for innate immune responses.

Area of Science:

  • Immunology
  • Materials Science
  • Nanotechnology

Background:

  • Monocytes/macrophages are key immune cells involved in innate immunity.
  • Monocytes/macrophages extracellular traps (METs) are crucial for pathogen defense.
  • METs are composed of DNA fibers decorated with nuclear and cytoplasmic proteins.

Purpose of the Study:

  • To investigate the ability of charged polyhedral oligomeric silsesquioxanes (POSS) to induce METosis.
  • To understand the mechanisms underlying POSS-induced METosis.

Main Methods:

  • METs formation induced by lipopolysaccharide (positive control) and varying concentrations of POSS (positive and negative charges).
  • Visualization and quantification of METs using confocal microscopy and Sytox green staining.
  • Evaluation of oxidative stress, autophagy, and endocytosis involvement in POSS-induced METosis.

Main Results:

  • POSS, regardless of charge, dose-dependently induced MET release.
  • POSS internalization was identified as a prerequisite for MET induction.
  • Involvement of oxidative stress and autophagy in POSS-induced METosis was confirmed by significant reduction upon using ROS blockers and autophagy inhibitors.

Conclusions:

  • POSS induces extracellular trap production in human monocytes/macrophages.
  • The mechanism involves both oxidative and autophagic pathways.
  • POSS represents a potential modulator of innate immune responses via METosis.

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