title: Catastrophic inflammatory death of monocytes and macrophages by overtaking of a critical dose of endocytosed synthetic amorphous silica nanoparticles/serum protein complexes.
abstract: OBJECTIVE
  We tested whether phagocytic monocytes/macrophages are more susceptible than nonphagocytes to nanoparticle (NP) toxicity.
  
  
  METHODS
  We compared in vitro cell death and proinflammatory cytokine production in human monocytes, macrophages, lymphocytes and HeLa cells due to synthetic amorphous silica (SiO2)-NPs in different serum concentrations and correlated them with cellular uptake and distribution.
  
  
  RESULTS
  Phagocytes were approximately ten-times more sensitive than nonphagocytes to SiO2-NPs and more effectively endocytosed SiO2-NP-serum protein nanoagglomerates, so determining their accumulation in acidic endocytic compartments well beyond a critical/cytotoxic threshold. Monocyte/macrophage death was paralleled by cytokine secretion.
  
  
  CONCLUSIONS
  The physiological specialization of monocytes/macrophages to effectively capture NPs may expose them to the risk of catastrophic inflammatory death upon saturation of their maximal storage capacity.
authors.affiliation: Centro di Ricerca Interdipartimentale per le Biotecnologie Innovative, Università di Padova, via U. Bassi 58/B, Padua, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fedeli
authors.forename: Francesco
authors.initials: F
authors.lastname: Selvestrel
authors.forename: Regina
authors.initials: R
authors.lastname: Tavano
authors.forename: Daniela
authors.initials: D
authors.lastname: Segat
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mancin
authors.forename: Emanuele
authors.initials: E
authors.lastname: Papini
mesh_terms: D001798:Blood Proteins / Q000737:chemistry* / Q000494:pharmacology; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D010586:Phagocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D012822:Silicon Dioxide