Inflammatory mechanism induced by natural and engineered silica particles in human-derived macrophages at low non-cytotoxic doses

摘要: Particle size, phase, and transition metals have all been implicated in natural engineered silica-induced respiratory effects, as well cellular interactions. However, efforts to unambiguously determine their role the pro-inflammatory mechanism induction hampered due use of inhomogeneous samples, with incomplete characterization high cytotoxic doses. Here, micro- nano- sized silica particles, which are more homogenous materials properties used a variety applications, were characterized compared at realistic dose level. Natural (2 μm) particles μm 50 nm) controlled for morphology, iron presence, surface area, aggregation. A novel lipid peroxidation-dependent influence iron, particle phase was hypothesized these under low non-cytotoxic closer exposure regime. It observed that 1 μg/ml presence or addition reduction crystalline significantly increased superoxide (O2.-) hydrogen peroxide (H2O2) production macrophages. This increase O2.- H2O2 production, further lead phosphatidylcholine-specific phospholipase C (PC-PLC) - mediated inflammatory mediator cytokine macrophages via peroxidation raft disruption (large fraction sub-domains plasma membrane involved signal transduction). Addition an chelator abrogated responses, supporting mechanism. Activation PC-PLC induced response determined by using inhibitor, Tricychodecan-9-yl-xanthate, blocked production. Microscopy studies cell-particle interaction revealed size also influenced uptake mainly phagocytosis, since binding activation receptors subsequent internalization is strongly dependent on nanoparticle size. Also, 100 showed macrophage overload both sizes, damage possibly leading catastrophic release mediators could obfuscate study normal response, emphasizing need In summary, this work demonstrated dependent-inflammatory PC-PLC. should better understanding important parameters particle-induced lungs, therefore, control effects caused real-life particles.