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Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice.

Authors
Shvedova-AA; Kisin-ER; Mercer-R; Murray-AR; Johnson-VJ; Potapovich-AI; Tyurina-YY; Gorelik-O; Arepalli-S; Schwegler-Berry-D; Hubbs-AF; Antonini-J; Evans-DE; Ku-BK; Ramsey-D; Maynard-A; Kagan-VE; Castranova-V; Baron-P
Source
Am J Physiol, Lung Cell Mol Physiol 2005 Nov; 289(5):L698-L708
NIOSHTIC No.
20028674
Abstract
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.
Keywords
Laboratory-animals; Animals; Animal-studies; Pulmonary-system-disorders; Respiratory-system-disorders; Fibrosis; In-vitro-studies; Nanotechnology
CODEN
APLPE7
Publication Date
20051101
Document Type
Journal Article
Email Address
AShvedova@cdc.gov
Funding Type
Grant
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
5
ISSN
1040-0605
NIOSH Division
HELD; DART
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
WV; OH; PA
Performing Organization
University of Pittsburgh at Pittsburgh
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