Pyrogenic and Precipitated Amorphous Silica Nanoparticles Differentially Affect Cell Responses to LPS in Human Macrophages

Bianchi, Massimiliano G.; Chiu, Martina; Taurino, Giuseppe; Ruotolo, Roberta; Marmiroli, Nelson; Bergamaschi, Enrico; Cubadda, Francesco; Bussolati, Ovidio

doi:10.3390/nano10071395

Cited by 7 publications

(16 citation statements)

References 55 publications

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“…However, for most SAS, the half maximal effective concentration (EC50) for several endpoints is comparatively low under protein-free conditions (e.g., 10–20 µg/mL for the release of LDH) [ 18 ], a finding which does not correspond to the in vivo effects of SAS especially when effects of amorphous and crystalline silica are compared [ 12 ]. On the other hand, the bioactivity of SAS in vitro is strongly reduced when particles (i) are administered in the presence of serum [ 20 ], (ii) are protein-treated prior to exposure [ 21 , 22 , 23 , 24 ] or (iii) are dispersed by extensive ultrasonic energy in the presence of low concentrations of albumin [ 25 ]. All aforementioned protein-treatments inevitably lead to the formation of a protein corona [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Lowers Bioactivity and Uptake of Synthetic Amorphous Silica by Alveolar Macrophages in a Particle Specific Manner

Wiemann¹,

Vennemann²,

Venzago

et al. 2021

Nanomaterials

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Various cell types are compromised by synthetic amorphous silica (SAS) if they are exposed to SAS under protein-free conditions in vitro. Addition of serum protein can mitigate most SAS effects, but it is not clear whether this is solely caused by protein corona formation and/or altered particle uptake. Because sensitive and reliable mass spectrometric measurements of SiO2 NP are cumbersome, quantitative uptake studies of SAS at the cellular level are largely missing. In this study, we combined the comparison of SAS effects on alveolar macrophages in the presence and absence of foetal calf serum with mass spectrometric measurement of 28Si in alkaline cell lysates. Effects on the release of lactate dehydrogenase, glucuronidase, TNFα and H2O2 of precipitated (SIPERNAT® 50, SIPERNAT® 160) and fumed SAS (AEROSIL® OX50, AEROSIL® 380 F) were lowered close to control level by foetal calf serum (FCS) added to the medium. Using a quantitative high resolution ICP-MS measurement combined with electron microscopy, we found that FCS reduced the uptake of particle mass by 9.9% (SIPERNAT® 50) up to 83.8% (AEROSIL® OX50). Additionally, larger particle agglomerates were less frequent in cells in the presence of FCS. Plotting values for lactate dehydrogenase (LDH), glucuronidase (GLU) or tumour necrosis factor alpha (TNFα) against the mean cellular dose showed the reduction of bioactivity with a particle sedimentation bias. As a whole, the mitigating effects of FCS on precipitated and fumed SAS on alveolar macrophages are caused by a reduction of bioactivity and by a lowered internalization, and both effects occur in a particle specific manner. The method to quantify nanosized SiO2 in cells is a valuable tool for future in vitro studies.

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Section: Introductionmentioning

confidence: 99%

Serum Lowers Bioactivity and Uptake of Synthetic Amorphous Silica by Alveolar Macrophages in a Particle Specific Manner

Wiemann¹,

Vennemann²,

Venzago

et al. 2021

Nanomaterials

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“…For example, ASNPs potentiate activation by LPS, at least in terms of NO production, of murine macrophage Raw 264.7 cells [17]. More recently, we have shown that exposure to low doses of ASNP interferes with the induction of glutamine synthetase, a change potentially related to macrophage polarization [18], and delays IL-1β secretion in LPS-treated THP-1 human macrophage-like cells [19]. In both cases, pyrogenic NM-203 ASNPs produced larger effects than the precipitated NM-200 ASNPs, confirming their higher bioreactivity observed in studies with other cell models [17,19].…”

Section: Introductionmentioning

confidence: 88%

“…More recently, we have shown that exposure to low doses of ASNP interferes with the induction of glutamine synthetase, a change potentially related to macrophage polarization [18], and delays IL-1β secretion in LPS-treated THP-1 human macrophage-like cells [19]. In both cases, pyrogenic NM-203 ASNPs produced larger effects than the precipitated NM-200 ASNPs, confirming their higher bioreactivity observed in studies with other cell models [17,19]. These data suggest that the interaction of ASNP with innate immune cells may have more complex effects than pro-inflammatory activation, such as alterations in the time course and features of the cell response to LPS.…”

Section: Introductionmentioning

confidence: 99%

“…Although being of human origin and widely used in nanotoxicological studies on ASNP [19][20][21][22][23][24][25], THP-1 macrophages have some limitations when fine biological mechanisms underlying the inflammatory response are to be investigated. Indeed, besides being a leukemic cell line, THP-1 attain a macrophage-like phenotype and pro-inflammatory competences only if differentiated with phorbol esters such as phorbol myristate acetate (PMA).…”

Section: Introductionmentioning

confidence: 99%

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The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles

et al. 2022

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Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the response of innate immunity cells to natural activators has not been thoroughly investigated. Here, we study the effects of pyrogenic ASNP on the LPS-dependent activation of human macrophages differentiated from peripheral blood monocytes. In macrophages, 24 h of pre-exposure to non-cytotoxic doses of ASNP markedly inhibited the LPS-dependent induction of pro-inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10). The inhibitory effect was associated with the suppression of NFκB activation and the increased intracellular sequestration of the TLR4 receptor. The late induction of glutamine synthetase (GS) by LPS was also prevented by pre-exposure to ASNP, while GS silencing did not interfere with cytokine secretion. It is concluded that (i) macrophages exposed to ASNP are less sensitive to LPS-dependent activation and (ii) GS induction by LPS is likely secondary to the stimulation of cytokine secretion. The observed interference with LPS effects may point to a dampening of the acute inflammatory response after exposure to ASNP in humans.

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“…Based on those differences it is assumed that pyrogenic SAS causes the highest toxicity (van Kesteren et al 2015). This is strengthened by in vitro studies demonstrating a more pronounced effect for pyrogenic SAS compared to precipitated SAS (Bianchi et al 2020). But surface modification or changes in shape may also affect toxicokinetic behavior and toxicity.…”

Section: Silica Usedmentioning

confidence: 99%

Issues currently complicating the risk assessment of synthetic amorphous silica (SAS) nanoparticles after oral exposure

et al. 2021

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Synthetic amorphous silica (SAS) is applied in food products as food additive E 551. It consists of constituent amorphous silicon dioxide (SiO 2 ) nanoparticles that form aggregates and agglomerates. We reviewed recent oral toxicity studies with SAS. Some of those report tissue concentrations of silicon (Si). The results of those studies were compared with recently determined tissue concentrations of Si (and Si-particles) in human postmortem tissues. We noticed inconsistent results of the various toxicity studies regarding toxicity and reported tissue concentrations, which hamper the risk assessment of SAS. A broad range of Si concentrations is reported in control animals in toxicity studies. The Si concentrations found in human postmortem tissues fall within this range. On the other hand, the mean concentration found in human liver is higher than the reported concentrations causing liver effects in some animal toxicity studies after oral exposure to SAS. Also higher liver concentrations are observed in other, negative animal studies. Those inconsistencies could be caused by the presence of other Si-containing chemical substances or particles (which potentially also includes background SAS) and/or different sample preparation and analytical techniques that were used. Other factors which could explain the inconsistencies in outcome between the toxicity studies are the distinct SAS used and different dosing regimes, such as way of administration (dietary, via drinking water, oral gavage), dispersion of SAS and dose. More research is needed to address these issues and to perform a proper risk assessment for SAS in food. The current review will help to progress research on the toxicity of SAS and the associated risk assessment.

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Pyrogenic and Precipitated Amorphous Silica Nanoparticles Differentially Affect Cell Responses to LPS in Human Macrophages

Cited by 7 publications

References 55 publications

Serum Lowers Bioactivity and Uptake of Synthetic Amorphous Silica by Alveolar Macrophages in a Particle Specific Manner

Serum Lowers Bioactivity and Uptake of Synthetic Amorphous Silica by Alveolar Macrophages in a Particle Specific Manner

The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles

Issues currently complicating the risk assessment of synthetic amorphous silica (SAS) nanoparticles after oral exposure

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