Effect of silica and gold nanoparticles on macrophage proliferation, activation markers, cytokine production, and phagocytosis in vitro

Abstract

The accumulation of durable nanoparticles (NPs) in macrophages following systemic administration is well described. The ultimate biological impact of this accumulation on macrophage function, however, is not fully understood. In this study, nontoxic doses of two durable NPs, SiO 2 and Au, at particle sizes of ~10 nm and 300 nm were used to evaluate the effect of bioaccumulation on macrophage function in vitro using RAW 264.7 mouse macrophage-like cells as a model system. Cell proliferation, cell cycle, cytokine production, surface marker activation, and phagocytosis responses were evaluated through a panel of assays using flow cytometry and confocal microscopy. The most dramatic change in RAW 264.7 cell function was a reduction in phagocytosis as monitored by the uptake of Escherichia coli . Cells exposed to both 10 nm Au NPs and 10 nm SiO 2 NPs showed ~50% decrease in phagocytosis, while the larger NPs caused a less dramatic reduction. In addition to modifying phagocytosis profiles, 10 nm SiO 2 NPs caused changes in proliferation, cell cycle, and cell morphology. Au NPs had no effect on cell cycle, cytokine production, or surface markers and caused interference in phagocytosis in the form of quenching when the assay was performed via flow cytometry. Confocal microscopy analysis was used to minimize this interference and demonstrated that both sizes of Au NPs decreased the phagocytosis of E. coli . Overall, our results demonstrate that Au and SiO 2 NP uptake by macrophages can influence macrophage phagocytosis in vitro without altering surface markers and cytokine production in vitro. While the biological impact of these findings remains unclear, our results indicate that bioaccumulation of durable NPs within the macrophages may lead to a suppression of bacterial uptake and possibly impair bactericidal activity.

Impact of Gold Nanoparticles on the Functions of Macrophages and Dendritic Cells

“…We showed that AuNPs by themselves did not fuel any cytokine secretion. These data are in the direct line of previous studies on DCs [14] and on M [24], indicating that AuNPs do not promote production of TNF-α, IL-6 and IL-10. These ndings were also validated by other previous publications in various models [23,26].…”

“…One of the key point of APCs is their ability to engulf foreign material by phagocytosis. The exposure to 10 nm AuNPs was shown to signi cantly reduce the phagocytic capacity of Raw 264.7 M cell line and BMDMs [24]. In the present study, we show that the phagocytic capacity of J774.1A M cell line is not impaired after 24 h exposure with AuNPs.…”

“…In the present study, we show that the phagocytic capacity of J774.1A M cell line is not impaired after 24 h exposure with AuNPs. A possible explanation for these different effects could be that different cell lines of M were used and /or to the nature of the phagocytosis assay that is based on the use of E coli [24] and of polystyrene beads in our study.…”

Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development

“…The most recent studies involving AuNPs demonstrate the effects of gold sodium thiomalate on macrophage function, showing lysosomal enzyme inhibition and reducing phagocytosis (37). Similar effects were seen in macrophages of several origins, which, when stimulated with AuNPs, showed diminished bactericidal activity against Staphylococcus aureus (38) and low or absent cytokine production IL-6, IL-10, and TNF-α (39, 40). Moreover, when splenocytes were stimulated with LPS, the addition of AuNP reduced IL-17 and TNF-α release (40).…”

The Current State of Nanoparticle-Induced Macrophage Polarization and Reprogramming Research

“…In this study, Ag NPs elicited a significant increase of NF-κB while Au NPs showed no activation of NF-κB and the inflammatory response induced by Ag NPs was similar to that induced by LPS. In several other studies, Au NPs were also not observed to induce the expression of M1 related markers [50,51,52]. According to available literature, different pro-inflammatory effects of Au NPs in macrophages were related with the length of exposure time.…”