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Carbon nanotubes induce immune suppression via direct effects on dendritic cells.
Tkach A; Shurin GV; Shurin MR; Kisin ER; Murray AR; Young SH; Star A; Fadeel B; Kagan VE; Shvedova AA
Toxicologist 2012 Mar; 126(Suppl 1):276
Mounting evidence indicates that exposure to nanoparticles (NP) is able to modify immune responses. However, cellular and molecular mechanisms of immune responses elicited by NP are poorly understood. In the current study, we evaluated site-specific pulmonary inflammation and systemic immune response in mice after pulmonary exposure to single walled carbon nanotubes (SWCNT). SWCNT exposure caused inflammation, pulmonary damage and an altered cytokine network in the lung. SWCNT-induced inflammation facilitated the recruitment of dendritic cells (DC) to the lung tissues, increasing chances of direct DC/SWCNT interactions. Local inflammatory response in vivo was accompanied by modified systemic immunity as documented by decreased proliferation of splenic T cells. To assess if DC could be responsible for modulation of systemic immunity in SWCNT-treated mice, we evaluated the ability of SWCNT-exposed DC to alter T cell responses in vitro. Here we demonstrate that co-culturing of T cells with SWCNT- exposed DC suppressed the T cell proliferation response upon re-stimulation with freshly generated, unexposed DC. Further, exposure of DC to SWCNT did not alter DC phenotype. Exposure of DC to E. coli LPS induced phenotypical maturation of DC. When LPS-exposed DC were mixed with T cells we observed facilitated T cell proliferation. Administration of LPS + SWCNT to DC did not change LPS-induced DC phenotypical maturation. Indeed, when T cells were mixed with LPS+SWCNT treated DC we observed decreased proliferation. Combined, these findings suggest that SWCNT do not interfere with recognition of LPS by DC. We can speculate that SWCNT exposure may intervene with antigen capture/processing and/or presentation, thereby leading to compromised DC/T cell interactions. Overall, our data suggest that exposure to SWCNT modifies systemic immunity by modulating DC function.
Nanotechnology; Health-hazards; Immune-system; Immune-reaction; Cell-function; Cellular-reactions; Molecular-biology; Laboratory-testing; Laboratory-animals; Pulmonary-function; Pulmonary-system; Cytotoxic-effects; Lung-cells; Lung-function; Cell-damage; Lung-tissue; In-vivo-study
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
PA; WV; CA
University of Pittsburgh at Pittsburgh
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