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Research Article

Catastrophic inflammatory death of monocytes and macrophages by overtaking of a critical dose of endocytosed synthetic amorphous silica nanoparticles/serum protein complexes

    Chiara Fedeli

    Centro di Ricerca Interdipartimentale per le Biotecnologie Innovative, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy

    Dipartimento di Scienze Biomediche, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy

    ,
    Francesco Selvestrel

    Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, I -35131 Padova, Italy

    ,
    Regina Tavano

    Centro di Ricerca Interdipartimentale per le Biotecnologie Innovative, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy

    Dipartimento di Scienze Biomediche, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy

    ,
    Daniela Segat

    Dipartimento di Biologia, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy

    ,
    Fabrizio Mancin

    Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, I -35131 Padova, Italy

    &
    Emanuele Papini

    * Author for correspondence

    Centro di Ricerca Interdipartimentale per le Biotecnologie Innovative, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy. .

    Dipartimento di Scienze Biomediche, Università di Padova, via U. Bassi 58/B, I-35131, Padova, Italy

    Published Online:https://doi.org/10.2217/nnm.12.136

    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

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

    References

    • Krug HF, Wick P. Nanotoxicology: an interdisciplinary challenge. Angew. Chem. Int. Ed. Engl.50(6),1260–1278 (2011).
    • Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ. Health Perspect.113(7),823–839 (2005).
    • Lunov O, Syrovets T, Loos C et al. Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. ACS Nano5(3),1657–1669 (2011).
    • Hornung V, Bauernfeind F, Halle A et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol.9(8),847–856 (2008).▪▪ Shows the mechanism of NALP3 inflammasome activation in macrophages by silica crystals.
    • Gilberti RM, Joshi GN, Knecht DA. The phagocytosis of crystalline silica particles by macrophages. Am. J. Respir. Cell Mol. Biol.39(5),619–627 (2008).
    • Park EJ, Park K. Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol. Lett.184(1),18–25 (2009).
    • Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH. The nanosilica hazard: another variable entity. Part. Fibre Toxicol.7(1),39 (2010).
    • Xie G, Sun J, Zhong G, Shi L, Zhang D. Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch. Toxicol.84(3),183–190 (2010).
    • Drescher D, Orts-Gil G, Laube G et al. Toxicity of amorphous silica nanoparticles on eukaryotic cell model is determined by particle agglomeration and serum protein adsorption effects. Anal. Bioanal. Chem.400(5),1367–1373 (2011).▪ Possible protective mechanism of serum against nanoparticle (NP) cytotoxicity is presented.
    • 10  Ye Y, Liu J, Chen M, Sun L, Lan M. In vitro toxicity of silica nanoparticles in myocardial cells. Environ. Toxicol. Pharmacol.29(2),131–137 (2010).
    • 11  Liu X, Sun J. Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappaB pathways. Biomaterials31(32),8198–8209 (2010).▪ Detailed analysis of the adverse effects induced by silica NPs on the first biological barrier encountered.
    • 12  Chang JS, Chang KL, Hwang DF, Kong ZL. In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ. Sci. Technol.41(6),2064–2068 (2007).
    • 13  Lin W, Huang YW, Zhou XD, Ma Y. In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicol. Appl. Pharmacol.217(3),252–259 (2006).
    • 14  Rabolli V, Thomassen LC, Uwambayinema F, Martens JA, Lison D. The cytotoxic activity of amorphous silica nanoparticles is mainly influenced by surface area and not by aggregation. Toxicol. Lett.206(2),197–203 (2011).
    • 15  Mohamed BM, Verma NK, Prina-Mello A et al. Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity. J. Nanobiotechnology9,29 (2011).
    • 16  Herd HL, Malugin A, Ghandehari H. Silica nanoconstruct cellular toleration threshold in vitro. J. Control. Release153(1),40–48 (2011).
    • 17  Costantini LM, Gilberti RM, Knecht DA. The phagocytosis and toxicity of amorphous silica. PLoS ONE6(2),e14647 (2011).
    • 18  Al-Rawi M, Diabate S, Weiss C. Uptake and intracellular localization of submicron and nano-sized SiO2 particles in HeLa cells. Arch. Toxicol.85(7),813–826 (2011).
    • 19  Stayton I, Winiarz J, Shannon K, Ma Y. Study of uptake and loss of silica nanoparticles in living human lung epithelial cells at single cell level. Anal. Bioanal. Chem.394(6),1595–1608 (2009).
    • 20  Panas A, Marquardt C, Nalcaci O et al. Screening of different metal oxide nanoparticles reveals selective toxicity and inflammatory potential of silica nanoparticles in lung epithelial cells and macrophages. Nanotoxicology doi:10.3109/17435390.652206) (2012) (Epub ahead of print).▪▪ Exhaustive comparative study on the cellular effects of various NP types showing that the intrinsic toxicity and proinflammatory potential of amorphous SiO2-NPs on murine macrophages are affected by fetal calf serum.
    • 21  Tavano R, Franzoso S, Cecchini P et al. The membrane expression of Neisseria meningitidis adhesin A (NadA) increases the proimmune effects of MenB OMVs on human macrophages, compared with NadA- OMVs, without further stimulating their proinflammatory activity on circulating monocytes. J. Leukoc. Biol.86(1),143–153 (2009).
    • 22  Franzoso S, Mazzon C, Sztukowska M et al. Human monocytes/macrophages are a target of Neisseria meningitidis adhesin A (NadA). J. Leukoc. Biol.83(5),1100–1110 (2008).
    • 23  Leanza L, Henry B, Sassi N et al. Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak-independent death of cancer cells. EMBO Mol. Med.4(7),577–593 (2012).
    • 24  Nuutila J, Lilius EM. Flow cytometric quantitative determination of ingestion by phagocytes needs the distinguishing of overlapping populations of binding and ingesting cells. Cytometry A65(2),93–102 (2005).
    • 25  Lu X, Qian J, Zhou H et al.In vitro cytotoxicity and induction of apoptosis by silica nanoparticles in human HepG2 hepatoma cells. Int. J. Nanomedicine6,1889–1901 (2011).▪▪ Detailed study on the difference between apoptosis induced by silica NPs in normal and tumoral hepatic cells.
    • 26  Ye Y, Liu J, Xu J, Sun L, Chen M, Lan M. Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line. Toxicol. In Vitro24(3),751–758 (2010).
    • 27  Miao EA, Rajan JV, Aderem A. Caspase-1-induced pyroptotic cell death. Immunol. Rev.243(1),206–214 (2011).
    • 28  Ohkuma S, Poole B. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc. Natl Acad. Sci. USA75(7),3327–3331 (1978).
    • 29  Hamilton RF Jr, Thakur SA, Mayfair JK, Holian A. MARCO mediates silica uptake and toxicity in alveolar macrophages from C57BL/6 mice. J. Biol. Chem.281(45),34218–34226 (2006).▪▪ Interesting study demonstrating the role of a scavenger receptor in silica particles’ interaction with murine alveolar macrophages.
    • 30  Thakur SA, Hamilton R Jr, Pikkarainen T, Holian A. Differential binding of inorganic particles to MARCO. Toxicol. Sci.107(1),238–246 (2009).
    • 31  Morishige T, Yoshioka Y, Inakura H et al. The effect of surface modification of amorphous silica particles on NLRP3 inflammasome mediated IL-1beta production, ROS production and endosomal rupture. Biomaterials31(26),6833–6842 (2010).
    • 32  Waters KM, Masiello LM, Zangar RC et al. Macrophage responses to silica nanoparticles are highly conserved across particle sizes. Toxicol. Sci.107(2),553–569 (2009).