Unusual Inflammatory and Fibrogenic Pulmonary Responses to Single-Walled Carbon Nanotubes in Mice

Details

• Personal Author:
  Antonini J ; Arepalli S ; Baron, Paul A. ; Castranova, Vincent ; Evans DE ; Gorelik O ; Hubbs, Ann F. ; Johnson VJ ; Kagan VE ; Kisin ER ; Ku BK ; Maynard A ; Mercer R ; Murray AR ; Potapovich AI ; Ramsey D ; Schwegler-Berry D ; Shvedova AA ; Tyurina YY
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Fibrosis Laboratories Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Animal-studies In-vitro-studies Laboratory-animals Nanotechnology Pulmonary-system-disorders Respiratory-system-disorders
• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 3 ; OSHA Region 5 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  289
• Issue:
  5
• NIOSHTIC Number:
  nn:20028674
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2005 Nov; 289(5):L698-L708
• Email:
  AShvedova@cdc.gov
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:85d64b9e0de6938882dc8b4abd92323ef9a8c9c78860830381d9dca1961501f76d493ccc8b4e36fe3aae906bbf55ab70e2e7aad8ef2e18a42b7b5b79e6f9c012
• Download URL:
  https://stacks.cdc.gov/view/cdc/189880/cdc_189880_DS1.pdf
• File Type:
  [PDF - 542.57 KB ]