SiO(2) nanoparticles as disruptors of endogenous resolution mechanisms of inflammatory responses that exacerbate pneumonia.

Occupational exposure to engineered nanomaterials (ENMs) is increasing in the workplace and can impact human health. Amorphous silicon dioxide nanoparticles (SiO(2) NPs) are widely produced respirable ENMs used in commercial products. We have investigated their impact on lung inflammation resolution and bacterial defense. Mice exposed to SiO(2) NPs, followed by bacteria, exhibited increased lung inflammation, bacterial proliferation, and lung damage compared to mice not exposed to NPs. SiO(2) NPs increased human macrophage production of pro-inflammatory mediators and disrupted phagocytosis of bacteria and efferocytosis of apoptotic neutrophils - pivotal responses for host defense and inflammation resolution. A pro-resolving mediator, resolvin D5 (RvD5), restored macrophage phagocytosis of bacteria and partially controlled excess lung inflammation after SiO(2) NPs. These findings demonstrate that SiO(2) NPs disrupt endogenous resolution processes to give rise to heightened lung inflammation and infection. RvD5 reduced inflammation and partially restored endogenous resolution cellular processes, suggesting that RvD5 can reduce ENP disruption of resolution.