Pulmonary exposure to carbonaceous nanoparticles affects local and systemic immunity.
Tkach-A; Kisin-E; Murray-AR; Shurin-GV; Shurin-MR; Young-SH; Star-A; Fadeel-B; Kagan-VE; Shvedova-AA
Toxicologist 2011 Mar; 120(Suppl 2):254
Numerous studies have focused on the toxicity associated with nanoparticle (NP) exposure. The results of studies on rodents have demonstrated that NP are capable of inducing inflammation, granulomas, fibrosis, and mutagenicity found in the lungs. However, immunologic effects of inhaled nanoparticles remain largely unexplored. In the current study, we evaluated the inflammatory response in the lung and systemic immune effects induced by pulmonary exposure to 40-120 ug/mouse of pristine (C60) or functionalized (C60-TRIS) fullerenes or single-walled carbon nanotubes (SWCNT). We demonstrated that pharyngeal aspiration of the studied NP caused inflammation and pulmonary damage as evidenced by accumulation of PMNs, changes in lung permeability and cell damage. In addition, NP stimulated release of pro-inflammatory and regulatory cytokines in the lung. Further, local inflammatory response was translated into suppressed systemic immunity as evidenced by 25% decrease in proliferation of splenic T cells stimulated by allogeneic dendritic cells (DC). To investigate possible mechanisms of compromised systemic immunity, we evaluated the ability of NP to directly affect stimulatory/polarizing activities of conventional DC (cDC) towards T cells in vitro. Exposure of cultured cDC to NP resulted in an impaired ability to stimulate T cells in an allogeneic MLR assay (up to 4-fold suppression). This effect was due to neither altered expression of CD80, CD86 or MHCII on DC as exhibited by DC phenotyping, nor by increased production of IL-10. Thus, mechanisms of altered systemic immunity in treated mice might be, at least in part, due to the direct effects of NP on cDC. Overall, our data suggest that NP affect and trigger both local and systemic immune responses in mice.
Biological-effects; Cancer; Carcinogenicity; Cell-biology; Cell-function; Cell-metabolism; Cell-morphology; Cell-transformation; Cellular-reactions; Exposure-assessment; Humans; Immune-system; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-cells; Lung-disease; Lung-disorders; Lung-irritants; Medical-research; Mutagenesis; Mutagens; Nanotechnology; Physiological-effects; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
University of Pittsburgh at Pittsburgh