Shvedova, A. A. et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 289, L698-L708

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
AJP Lung Cellular and Molecular Physiology (Impact Factor: 4.08). 12/2005; 289(5):L698-708. DOI: 10.1152/ajplung.00084.2005
Source: PubMed


Single-walled carbon nanotubes (SWCNT) are new materials of emerging technological importance. As SWCNT are introduced into the life cycle of commercial products, their effects on human health and environment should be addressed. We demonstrated that pharyngeal aspiration of SWCNT elicited unusual pulmonary effects in C57BL/6 mice that combined a robust but acute inflammation with early onset yet progressive fibrosis and granulomas. A dose-dependent increase in the protein, LDH, and gamma-glutamyl transferase activities in bronchoalveolar lavage were found along with accumulation of 4-hydroxynonenal (oxidative biomarker) and depletion of glutathione in lungs. An early neutrophils accumulation (day 1), followed by lymphocyte (day 3) and macrophage (day 7) influx, was accompanied by early elevation of proinflammatory cytokines (TNF-alpha, IL-1beta; day 1) followed by fibrogenic transforming growth factor (TGF)-beta1 (peaked on day 7). A rapid progressive fibrosis found in mice exhibited two distinct morphologies: 1) SWCNT-induced granulomas mainly associated with hypertrophied epithelial cells surrounding SWCNT aggregates and 2) diffuse interstitial fibrosis and alveolar wall thickening likely associated with dispersed SWCNT. In vitro exposure of murine RAW 264.7 macrophages to SWCNT triggered TGF-beta1 production similarly to zymosan but generated less TNF-alpha and IL-1beta. SWCNT did not cause superoxide or NO.production, active SWCNT engulfment, or apoptosis in RAW 264.7 macrophages. Functional respiratory deficiencies and decreased bacterial clearance (Listeria monocytogenes) were found in mice treated with SWCNT. Equal doses of ultrafine carbon black particles or fine crystalline silica (SiO2) did not induce granulomas or alveolar wall thickening and caused a significantly weaker pulmonary inflammation and damage.

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    • "In recent years, some types of ENMs have been shown to be hazardous to human health. It has been reported that carbon nanotubes (CNTs) are capable of inducing reactive oxygen species (ROS) (Sharma et al., 2007) and pulmonary effects (Shvedova et al., 2005). Toxicological studies have also shown that nanosized titanium dioxide (TiO 2 ) particles have the potential to induce cytotoxic (Saquib et al., 2012; Setyawati et al., 2012), genotoxic (Shukla et al., 2011; Trouiller, Reliene, Westbrook, Solaimani, & Schiestl, 2009), and inflammatory (Grassian, O'Shaughnessy, Adamcakova-Dodd, Pettibone, & Thorne, 2007; Han, Newsome, & Hennig, 2013) effects. "
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    • "The first set of experiments showed that pharyngeal aspiration of SWCNTs (10 µg/mouse) with low iron content led to increased pulmonary inflammation, lipid peroxidation and depletion of GSH in BALF (most pronounced at day 1 after exposure) and progressive development of fibrosis over a 28-day post-exposure period (Shvedova et al. 2005). Inhalation of SWCNTs with 18 % iron content (5 mg/ m 3 , 5 h/day for 4 days) also decreased the GSH level and increased levels of protein thiols and malondialdehyde in lung tissue of mice (Shvedova et al. 2008a). "
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