Catastrophic Inflammatory Death of Monocytes and Macrophages by Overtaking of A Critical Dose of Endocytosed Synthetic Amorphous Silica Nanoparticles/Serum Protein Complexes

Abstract

Aims: We tested whether phagocytic monocytes/macrophages are more susceptible than nonphagocytes to nanoparticle (NP) toxicity. Materials & 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. Conclusion: 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.

Original submitted 9 March 2012; Revised submitted 3 August 2012; Published online 13 December 2012

Keywords::

• amorphous silica
• cell death
• fetal calf serum
• inflammatory cytokines
• LUDOX^® SiO₂-NPs
• macrophages
• monocytes
• mononuclear phagocyte system
• nanoparticles
• reticular endothelial system
• Stöber SiO₂-NPs

Financial & competing interests disclosure

This research was supported by funding from the European Community‘s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 201031 NANOPHOTO, a grant by the University of Padova (Ex 60%, 2009–2010) and a grant by the University of Padova (PRAT 2011). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors thank the Centro Trasfusionale of the Hospital of Padua (ULSS 16) for providing buffy coats.

Additional information

Funding

This research was supported by funding from the European Community‘s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 201031 NANOPHOTO, a grant by the University of Padova (Ex 60%, 2009–2010) and a grant by the University of Padova (PRAT 2011). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.