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.