A study of mouse mast cells revealed significant division between the two engineered nanoparticles. SiO2 suppressed antigen-induced allergic activation in vitro, while mTiO2 showed cytotoxic and pro-inflammatory effects.
Research: Investigation of the immunomodulatory role of nanoparticles on mast cell activation. Image credit: Corona Borealis Studio / Shutterstock
In a recent study published in the journal scientific reportresearchers investigated how the physicochemical properties of engineered nanoparticles influence mast cell activation associated with skin hypersensitivity reactions. In this study, we evaluated the effects of negatively charged silica (SiO2) and manganese-doped titanium dioxide (mTiO2) nanoparticles on bone marrow-derived mast cells (BMMCs).
Study results revealed that mTiO2 NPs exhibited significant cytotoxic and pro-inflammatory effects, while SiO2 NPs were protected against antigen-induced mast cell activation. in vitro. In the presence of target antigen, SiO2 significantly suppresses mast cell degranulation and expression of activation markers, providing mechanistic insight into how selected nanoparticles modulate allergic immune responses.
Inquiring into the context of dermatitis and nanomaterials
Contact dermatitis is a common inflammatory skin disease, and current reports estimate that this condition affects up to 9.8% of the population and accounts for approximately 90% of occupational skin disorders in developed countries. Furthermore, these reports highlight that the clinical incidence of allergic contact dermatitis is increasing, with 17 new allergens being reported each year (2008–2015).
Unlike the more common irritant contact dermatitis (ICD), allergic contact dermatitis (ACD) is a delayed hypersensitivity reaction that begins when damage to the epidermal (skin) barrier allows entry of exogenous hapten sensitizers (such as nickel or latex).
Encouragingly, recent advances in engineered nanomaterials have shown that alive Studies have shown that small (<200 nm) negatively charged nanoparticles (NPs) can modulate adaptive immune responses. In this paper, we used a dinitrofluorobenzene mouse model of contact hypersensitivity (a surrogate for human ACD) and found that SiO2 NPs suppressed the allergic phenotype, whereas mTiO2 NPs exacerbated it.
Although this study highlighted the potential of nanomaterials in treating allergic conditions and skin diseases, the precise cellular mechanisms driving this differential immune modulation remained poorly understood.
bone marrow mast cells
The present study aimed to address this knowledge gap by focusing on the effects of these nanomaterials on mast cells expressing high-affinity FcεRI receptors bound to immunoglobulin E (IgE) that mediate allergic cascades.
This study specifically used bone marrow-derived mast cells (BMMCs) harvested and differentiated from the bone marrow of outbred SKH hairless mice over a 4-week culture period. Only BMMCs that showed >95% purity based on c-kit (CD117+) and FcεRI+ expression were included in the experimental matrix.
Two commercially available nanomaterials, negatively charged amorphous SiO2 NPs (average primary particle size 21.42 nm by transmission electron microscopy (TEM)) and negatively charged 1% mTiO2 NPs (56.02 nm) were used as experimental matrices.
The experimental procedure consisted of first sensitizing BMMCs using 1 μg/mL anti-dinitrophenyl (anti-DNP) IgE. Sensitized cells were then exposed to NPs alone or co-incubated with 100 ng/mL DNP-human serum albumin antigen to cross-link FcεRI receptors and model antigen-mediated mast cell activation.
The primary endpoints were measured using flow cytometry (for cell viability estimation), β-hexosaminidase release assay (for degranulation quantification), and cytokine secretion profiles (IL-6, IL-13, and TNF-α measured by enzyme-linked immunosorbent assay (ELISA)).
Finally, we used multiparametric flow cytometry to measure the median fluorescence intensity (MFI) of specific cell surface markers for activation and degranulation, such as FcεRI, CD117, CD63, and CD107a.
SiO2 and mTiO2 produce opposite effects
The estimation of cytotoxicity profile in this study demonstrated that mTiO2 induces significant cell death in a dose- and time-dependent manner. A brief 1 hour exposure to a concentration of >25 μg/mL was found to be sufficient to reduce BMMC viability by >30%.
In contrast, SiO2 showed remarkable biocompatibility and maintained 90% cell viability even after 24 h of incubation (100 μg/mL). TEM images confirmed that mTiO2 NPs (1 μg/mL) were actively endocytosed within 30 min, whereas no structural evidence of uptake was observed for SiO2 (10 μg/mL).
In the absence of antigen, mTiO2 acted as a cytotoxic and pro-inflammatory stressor, causing baseline degranulation at 25 μg/mL and upregulating TNF-α production after 24 h. Conversely, under allergen-stimulated conditions, SiO2 exerted a strong dose-dependent immunosuppressive effect.
Furthermore, SiO2 reduced DNP-induced IL-13 release after 24 h. In contrast, mTiO2 exerted pro-inflammatory effects and significantly amplified DNP-induced IL-6 release at both 4 and 24 h.
Phenotypic surface analysis verified these findings. DNP alone induced the expected activation kinetics by downregulating FcεRI and CD117 while upregulating lysosome-associated membrane proteins (CD63 and CD107a).
Co-exposure with SiO2 was shown to stop the downregulation of FcεRI and significantly reduce the surface expression spikes of CD63 and CD107a. In contrast, co-exposure with mTiO2 did not substantially alter DNP-driven FcεRI, CD117, or CD107a responses and slightly downregulated CD63.
Possibility of nanotherapy for allergic diseases
This study confirmed that nanoparticles can modulate early mast cell responses involving high-affinity IgE receptor pathways, although non-IgE mechanisms cannot be excluded. mTiO2 acts as an environmental stress factor with cytotoxic and pro-inflammatory effects, while SiO2 acts as a potent stress factor. in vitro Suppressor of antigen-induced mast cell activation.
However, it is limited to in vitro These findings provide a mechanistic framework for evaluating unknown compounds. Ultimately, this study could help design future nanotherapeutics for allergic conditions.
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