Long-term respiratory exposure to amorphous silica nanoparticles promoted systemic inflammation and progression of fibrosis in a susceptible mouse model

Exposure to amorphous silica nanoparticles (SiNPs) has increased dramatically, and concerns are growing about their potential health effects. However, their long-term systemic toxicity profile and underlying mechanisms following respiratory exposure still remains unexplored. It is well documented that the inhalation of ultrafine particles is firmly associated with adverse effects in humans. Environmental pollutants may contribute to diverse adverse effect or comorbidity in susceptible individuals. Thereby, we examined the long-term systemic effects of inhaled SiNPs using a sensitive mouse model (ApoE-/-) fed by a western diet. Male ApoE-/- mice were intratracheally instilled with SiNPs suspension at a dose of 1.5, 3.0 and 6.0 mg/kg·bw, respectively, once per week, 12 times in total. The histological analysis was conducted. The serum cytokine levels were quantified by RayBiotech antibody array. As a result, systemic histopathological alterations were noticed, mainly characterized by inflammation and fibrosis. More importantly, cytokine array analysis indicated the key role of mast cells accumulation in systemic inflammation and fibrosis progression induced by inhaled SiNPs. Collectively, our study firstly demonstrated that long-term exposure to inhaled SiNPs promoted the mast cell-dominated activation of inflammatory response, not only in the lung but also in heart, liver and kidney, etc., eventually leading to the progression of tissue fibrosis in ApoE-/- mice.