Exposure to silver nanoparticles primes mast cells for enhanced IgE/FcɛR1-mediated activation

Abstract

Abstract Nanotechnology has been greatly expanding over the past few years and engineered nanomaterials (ENM) are being employed into many consumer products; yet, a basic understanding about their potential associated adverse responses is largely lacking. Silver nanoparticles (AgNP) are one of the most utilized ENMs primarily for their antimicrobial properties. We recently demonstrated a non-IgE activation of signal transduction pathways including PI3K, PLCγ, PKC and calcium signaling leading to robust mast cell degranulation (early-phase response) following AgNP exposure. Here, we examined late-phase activation, reactive oxygen species (ROS) formation, stress response and IgE-induced activation following exposure to AgNPs. Our data revealed that, unlike IgE, exposure to 20 nm AgNP resulted in a delayed (24 hours) activation of the MAPK pathway without release of inflammatory cytokines. Although AgNPs induced transient ROS formation (within the first hour), long-term exposure (6, 24 hours) was neither associated with cellular stress response (e.g. glutathione levels) nor it involved apoptotic or necrotic cell death. Importantly, despite the lack of major AgNP toxicity, our results demonstrated that exposure to AgNPs primed mast cells for exacerbated IgE/FcɛR1 activation. Specifically, exposure to AgNPs for 24–72 hours resulted in enhanced IgE-mediated phosphorylation of FcɛR1-linked protein tyrosine kinases, degranulation, and cytokine release. Together, albeit exposure to AgNPs appeared non-toxic to mast cells, our findings suggest that AgNPs might prime mast cell for exacerbated allergic type responses and further investigation is warranted to understand the underlying mechanism.