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1 Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA
2 Division of Applied Research and Technology, NIOSH, Cincinnati, OH, USA
3 Center for Free Radical & Antioxidant Health and Department of Environmental Health, University of Pittsburgh, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: ats1{at}cdc.gov.
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, 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 (day 1), followed by lymphocyte (day 3) and macrophage (day 7) influx were accompanied by early elevation of pro-inflammatory cytokines (TNF-
, IL-1
, day 1) followed by fibrogenic TGF-1 (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 RAW264.7 macrophages to SWCNT triggered TGF-1 production similarly to zymosan but generated less TNF- and IL-1. SWCNT did not cause superoxide or NO. production, active SWCNT engulfment, or apoptosis in RAW264.7 macrophages. Functional respiratory deficiencies and decreased bacterial clearance (Listeria monocytogenes) were found in mice treated with SWCNT. Equal doses of ultrafine carbon black particles (UfCB) or fine crystalline silica (SiO2) did not induce granulomas, alveolar walls thickening, and caused a significantly weaker pulmonary inflammation and damage.
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