Pulmonary exposure to graphene oxide and fullerenes causes inflammation and modifies the immune response.
Stanley-SC; Tkach-AV; Shurin-MR; Shurin-GV; Kisin-E; Murray-AR; Pareso-S; Leonard-S; Young-SH; Fadeel-B; Mathur-S; Star-A; Kotchey-GP; Castranova-V; Kagan-VE; Shvedova-AA
Toxicologist 2012 Mar; 126(Suppl 1):145
Carbonaceous nanoparticles (CNP) have distinctive physical and chemical properties that make them useful in a wide range of applications. As the production of these particles increases, there is a growing need to explore their potentially harmful effects due to environmental and occupational exposure. Mounting evidence indicates that toxicological outcomes of CNP exposure may vastly depend on surface properties, size, shape and functionalization. In the current study, we evaluated pulmonary inflammation and systemic immune responses in mice after pulmonary exposure to structurally different CNP: pristine C60 fullerene; TRIS-functionalized C60 (C60-TRIS) and graphene oxide (GO). The inflammagenic potential of the tested CNP was found to be as follows: GO>C60-TRIS>C60, as evidenced by accumulation of PMNs, macrophages and lymphocytes as well as changes in lung permeability and inflammatory cytokine profiles in the lungs on days 1 and 7 post exposure. Further, GO and fullerenes were found to induce reactive oxygen species production by RAW 264.7 macrophages in vitro. To investigate if pulmonary exposure to CNP altered systemic immune reactivity, we tested the proliferative response of spleen T cells of exposed animals. In mice exposed to GO, T cell proliferation was decreased; however, it was increased in fullerene-exposed animals. Co-incubation of OVA-specific B3Z hybridoma T cells with OVA-loaded dendritic cells (DC) exposed to GO or fullerenes resulted in altered IL-2 production by B3Z cells, suggesting that modified T cells responses seen in vivo can be partially attributed to a direct modulation of DC functions by GO. Overall, our study shows the potential of fullerenes and GO to induce pulmonary inflammation.
Nanotechnology; Health-hazards; Toxic-materials; Toxic-effects; Surface-properties; Chemical-properties; Physical-properties; Immune-reaction; Immune-system; Pulmonary-function; Pulmonary-system; Laboratory-animals; Laboratory-testing; Lung-cells; Lung-function; Molecular-structure; Lymphocytes; Cell-wall-permeability; Cytotoxic-effects; Cell-alteration; Cell-division; In-vitro-study; In-vivo-study
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California