Nano-silica particles synergistically IgE-mediated mast cell activation exacerbating allergic inflammation in mice

Abstract

BackgroundAllergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied.MethodsFour common mineral elements with different particle sizes in smog particles were selected, including Al2O3, TiO2, Fe2O3, and SiO2. We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing.ResultsOnly 20 nm SiO2 particles significantly increased β-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan’s blue extravasation in mice was increased after treatment with nano-SiO2 particles. Nano-SiO2 particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO2 particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing β-hexosaminidase release.ConclusionOur results indicated that nano-SiO2 particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO2 particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases.

Toxicity and Mechanisms of Engineered Nanoparticles in Animals with Established Allergic Asthma

“…SiO 2 NPs could activate IgE-sensitized mast cells via enhancing the mitogen-activated protein kinase signaling pathway, which could worsen allergic inflammation. 40 These findings provide valuable information on potential therapeutic targets for the treatment of allergic asthma.…”

“… [ 39 ] SiO 2 Female Balb/c mice OVA 10 mg/kg 7 Tail vein injection Before and during challenge phase SiO 2 NPs exposure could exacerbate allergic inflammation. [ 40 ] SiO 2 Female Balb/c mice OVA 5, 10, 20 mg/kg 3 Intranasal instillation Before and during challenge phase SiO 2 NPs aggravated asthma development via inflammasome activation. [ 41 ] SiO 2 Female Balb/c mice OVA 10 mg/kg 6 Intranasal inoculation During sensitization and challenge phases SiO 2 NPs exerted adjuvant effect for OVA to induce allergic airway inflammation.…”

Molecular mechanisms and cellular process in signal transduction pathway related to air pollutants in obstructive lung diseases: A mini-review

“…SO 2 produces ROS and activates the TLR4/NF-κB pathway and can further augment IL-4 and IL-5 cytokine secretion and eosinophilic airway inflammation (Zhang et al, 2021a(Zhang et al, , 2021b. Nano-SiO 2 particles in the animal model of asthma might synergistically activate IgE-sensitization of mast cells through the MAPK signaling pathway and ERK1/2 phosphorylation, and nano-SiO 2 particles could incite airway inflammation (Yang et al, 2022).…”