Direct fibrogenic effects of dispersed single walled carbon nanotubes on human lung fibroblasts.
Wang L; Castranova V; Rojanasakul Y; Lu Y; Scabilloni JF; Mercer RR
Toxicologist 2008 Mar; 102(1):307
Nanomaterials, including single walled carbon nanotubes (SWCNT), are being developed for a variety of commercial products. However, toxicity of these new materials has not yet been identified due to limited information regarding the relationship between their unique physicochemical properties and potential toxicity. We reported recently that dispersed SWCNT (DSWCNT) exposure in mice caused a rapid and progressive interstitial lung fibrosis without a persistent inflammation. From these studies, it was hypothesized that DSWCNT, due to their exceptionally small size, can quickly penetrate the alveolar epithelial wall, enter the underlying tissue, and induce a "direct" fibrotic effect by interacting with cells at the site of particle accumulation to induce collagen deposition. The present study investigated the effects of in vitro DSWCNT exposure of human lung fibroblasts on proliferation and collagen production using cell multiplication (MTT), and Western blot techniques. DSWCNT were prepared using methods described previously in our laboratory. The results demonstrated that: 1) pulmonary exposure to DSWCNT (10 ug/mouse) did not cause significant lung injury; however, DSWCNT did penetrate into the interstitial lung tissue as analyzed by electron microscopy; 2) DSWCNT stimulated fibroblast cell growth in vitro at doses of 0.3-1 ug/ml; 3) DSWCNT also induced collagen production and collagenase (MMP9) activation in the treated fibroblasts. We also observed that the dispersion status or size of the SWCNT is a critical factor in determining fibrogenicity. These findings provide new insights into the mechanisms of SWCNT-induced lung fibrosis and may aid in developing models for risk assessment of these nanoparticles.
Cell-biology; Biological-factors; Biological-monitoring; Biological-effects; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Pulmonary-system; Laboratory-animals; Breathing; Inhalation-studies; Physical-chemistry; Lung-cells; Humans; Cellular-function; Cellular-respiration; Cell-metabolism; Cell-function; Cell-biology; Fibrogenicity; Fibrous-bodies; Fibrogenesis; Particulates; Particulate-dust; Nanotechnology
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington