Silver nanoparticles trigger delayed inflammatory responses in mast cells

Background : The rapid advancement of nanotechnology has led to a wide use of engineered nanomaterials (ENMs). Ensuring their safety remains critical for successful clinical translation. It was previously reported that administration of ferumoxytol (an FDA-approved iron oxide nanoparticle formulation) resulted in fatal anaphylactic reactions. Importantly, previous studies demonstrated that ENMs can induce mast cell early-phase activation, with 20 nm citrate-coated silver nanoparticles (AgNPs) producing a robust response. Purpose: This study investigated late-phase activation of mast cells following exposure to AgNPs in comparison to a classical IgE activation. Research Design: The study used murine bone marrow-derived mast cells (BMMCs) exposed to 20 nm citrate-coated AgNPs (25 μg/mL). Results: AgNP exposure induced late-phase BMMC activation, though this response was delayed and lower in magnitude compared to IgE activation. Specifically, exposure to AgNPs induced lipid mediator release (1h), and in some cases, showed differential regulation, with an overall lower magnitude of lipid release compared to IgE activation. Furthermore, AgNP exposure activated several inflammatory genes, with a delayed onset and reduced intensity relative to IgE stimulation. These data were reflected in the activation of mitogen-activated protein kinases (MAPKs) with significant changes occurring at later time points (24h). Importantly, no cytotoxicity or elevated levels of intracellular reactive oxygen species were observed, although Lamp-2 expression remained upregulated compared to IgE stimulation. Conclusion: The results suggest that AgNPs induce late-phase BMMC activation, potentially via a non-IgE-mediated mechanism characterized by a delayed and overall attenuated response. These findings underscore the importance of understanding ENM–bio interaction, not only for nanosafety, but also for unraveling novel therapeutic applications.