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Usual and unusual features of pulmonary responses to carbon nanotubes.

Kagan-VE; Shvedova-AA
First Annual Meeting of the American Academy of Nanomedicine, August 15-16, 2005, Baltimore, Maryland. Washington DC: American Academy of Nanomedicine, 2005 Aug; :26
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. 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, lactate dehydrogenase (LDH), and g-glutamyl transferase (GGT) activities in BAL were found along with accumulation of 4-hydroxynonenal (oxidative biomarker), and depletion of glutathione in lungs. An early neutrophils accumulation, followed by macrophage influx were accompanied by early elevation of proinflammatory cytokines. Early release of fibrogenic TGF-b1 was associated with 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 RAW264.7 macrophages to SWCNT triggered TGF-b1 production similarly to zymosan but generated less TNF-a and IL-1b. SWCNT did not cause superoxide or NO production, active SWCNT engulfment, or apoptosis in RAW264.7 macrophages. Equal doses of ultrafine carbon black particles or fine crystalline silica did not induce granulomas, alveolar walls thickening, and caused a significantly weaker pulmonary inflammation and damage. Based on our results, mechanism-based interventions may be developed to decrease toxicity of SWCNT.
Laboratory-animals; Animal-studies; Animals; Fibrosis; Pulmonary-system-disorders; Lung-disorders; Lung-fibrosis; Fibrogenicity; Fibrogenesis; Nanotechnology
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Abstract; Conference/Symposia Proceedings
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First Annual Meeting of the American Academy of Nanomedicine, August 15-16, 2005, Baltimore, Maryland
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