Abstract
Abstract Mast cells play a critical role in the initiation and propagation of several inflammatory diseases and are well known for their function in the allergic response. Fullerenes are a class of novel carbon allotropes with a wide variety of applications in biotechnology and medicine. Here we use a fullerene-based chemistry platform to develop and test several different fullerene derivatives to evaluate on cellular viability, anti-IgE receptor-mediated degranulation, and cytokine release from human skin mast cells (MC). The biological response depended on the properties of the addition group; some fullerene structures were effective inhibitors of degranulation and also blocked cytokine release, while others were ineffective. None were toxic to the cells using concentrations up to 100 µg/ml. Further, we demonstrate that mitochondrial membrane potential (MMP) closely paralleled IgE-mediated SMC degranulatory responses and this response was greatly inhibited by fullerene pre-incubation. Additionally, the fullerene inhibition was due to the inhibition of FcεRI-mediated MAP kinase activation. These findings suggest the biological properties of fullerene derivatives depends on the derivatization of the carbon cage which can be manipulated to compounds which may control those diseases associated with MC activation.
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