The Phagocytosis and Toxicity of Amorphous Silica

Abstract

BackgroundInhalation of crystalline silica is known to cause an inflammatory reaction and chronic exposure leads to lung fibrosis and can progress into the disease, silicosis. Cultured macrophages bind crystalline silica particles, phagocytose them, and rapidly undergo apoptotic and necrotic death. The mechanism by which particles are bound and internalized and the reason particles are toxic is unclear. Amorphous silica has been considered to be a less toxic form, but this view is controversial. We compared the uptake and toxicity of amorphous silica to crystalline silica.Methodology/Principal FindingsAmorphous silica particles are phagocytosed by macrophage cells and a single internalized particle is capable of killing a cell. Fluorescent dextran is released from endo-lysosomes within two hours after silica treatment and Caspase-3 activation occurs within 4 hours. Interestingly, toxicity is specific to macrophage cell lines. Other cell types are resistant to silica particle toxicity even though they internalize the particles.The large and uniform size of the spherical, amorphous silica particles allowed us to monitor them during the uptake process. In mCherry-actin transfected macrophages, actin rings began to form 1-3 minutes after silica binding and the actin coat disassembled rapidly following particle internalization. Pre-loading cells with fluorescent dextran allowed us to visualize the fusion of phagosomes with endosomes during internalization. These markers provided two new ways to visualize and quantify particle internalization. At 37°C the rate of amorphous silica internalization was very rapid regardless of particle coating. However, at room temperature, opsonized silica is internalized much faster than non-opsonized silica.Conclusions/SignificanceOur results indicate that amorphous and crystalline silica are both phagocytosed and both toxic to mouse alveolar macrophage (MH-S) cells. The pathway leading to apoptosis appears to be similar in both cases. However, the result suggests a mechanistic difference between FcγRIIA receptor-mediated and non-opsonized silica particle phagocytosis.

Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines

“…However, it was inhibitory to a number of cytokines in A549 cells. Similarly, crystalline or amorphous silica-based particles are highly cytotoxic in mouse alveolar macrophages (MH-S), while epithelial cell lines MLE, NIH-3T3, MDCK and HeLa are virtually resistant (Costantini et al, 2011). In the present study, CRI displayed low cytotoxic potency relative to SiNPs, however it had some impact at the highest dose of exposure in the macrophages.…”

“…The inhibition of G-CSF and the induction of IL-1ra, IL-4, IL-10 in THP-1 cells and IL-10, IL-13 in J774A.1 cells, alongside the overwhelmingly pro-inflammatory response in the macrophages highlight the complexity in the inflammatory and compensatory mechanisms in the presence of the silica-based particles. Exposures of macrophages to crystalline SiO 2 and amorphous SiNPs resulted in cell death (Costantini et al, 2011;Thibodeau et al, 2003). The mechanism involves the regulation of caspase-1 activity through the activation of the NALP3/inflammasome and the IL-1a/IL-1b-and TNF-a-induced inflammatory pathways triggered by SiO 2 (P etrilli et al, 2007; Rabolli et al, 2014).…”

Inhalation of Bacterial Cellulose Nanofibers Facilitates Silica Particle Clearance in a Rat Silicosis Model

“…Then twice daily for 30 consecutive days, starting three days after the injection of silica particles, each rat in the IBCN inhalation groups was sprayed with an aerosol containing homogenized BC with the appropriate IBCN content for one minute. Rats in the positive and negative control groups were sprayed with saline solution during this period in the same fashion: using fine sprays (of ICBN or saline solution) generated with a Yuyue 402AI ultrasonic nebulizer and nozzle (Jiangsu Yuyue Medical Equipment Ltd., Jiangsu, China) [13][14][15].…”

Immune System and Environmental Xenobiotics - The Effect of Selected Mineral Fibers and Particles on the Immune Response

“…In addition to nickel, workers in metal mining and processing are exposed to diesel emissions, oil mists, blasting agents and also to various other substances prevalent in the mine or industry (Lightfoot et al, 2010). Some of them, such as silica (Costantini et al, 2011;Huaux, 2007), radon (Chauhan et al, 2011) or arsenic (Burchiel at al. 2009) are known to be potent immunotoxic agents thus implicating possible synergistic effects on the immune response.…”