Examining the immunomodulatory role of nanoparticles on mast cell activation

Recent studies reveal that inorganic nanoparticles (NPs) can alter allergic skin reactions in a contact hypersensitivity (CHS) mouse model. Specifically, negatively charged silica (SiO₂) NPs suppressed the response whereas manganese doped titanium dioxide (mTiO₂) exacerbated it. Mast cells are critically important in transducing the CHS response. In this study we investigated the effect of SiO₂ and mTiO₂ NPs on bone marrow derived mast cell (BMMC) activation markers, degranulation and cytokine release. Sensitized BMMC were exposed to NPs alone or NPs plus antigen. Cytokines (IL-6, IL-13, TNF-α) and degranulation (β-hexosaminidase) studies were performed. Flow cytometry was used to follow cell surface activation markers including FcεRI, CD63 (LAMP-3), and CD107a (LAMP-1). Transmission Electron Microscopy (TEM) studies were preformed to assess NP endocytosis. Results found that mTiO₂ NPs were cytotoxic to BMMC in a dose- and time-dependent manner. SiO₂ NPs showed minimal cytotoxicity up to 100 µg/ml. In the absence of antigen the NPs had limited effect on sensitized BMMC degranulation or cytokine release. However, in the presence of antigen, 30 min co-culture studies (NP plus antigen) showed that SiO₂ NPs protect against degranulation, and they suppressed the expression of cell surface activation markers whereas mTiO₂ NPs exacerbated these.