Pathologic and molecular profiling of rapid-onset fibrosis and inflammation induced by multi-walled carbon nanotubes

Details

• Personal Author:
  Battelli LA ; Dong J ; Ma Q ; Porter DW ; Richardson DL ; Wolfarth MG
• Description:
  Multi-walled carbon nanotubes (MWCNT) are new materials with a wide range of industrial and commercial applications. However, their nano-scaled size and fiber-like shape render them respirable and potentially fibrogenic if inhaled into the lungs. To understand MWCNT fibrogenesis, we analyzed the pathologic and molecular aspects of the early phase response to MWCNT in mouse lungs. MWCNT induced rapid and pronounced lesions in the lungs characterized by increased cellularity and formation of fibrotic foci, most notably near where MWCNT deposited, within 14 days post-exposure. Deposition of collagen fibers was markedly increased in the alveolar septa and fibrotic foci, accompanied by elevated expression of fibrotic genes Col1a1, Col1a2, and Fn1 at both mRNA and protein levels. Fibrosis was induced rapidly at 40 ug, wherein fibrotic changes were detected on day 1 and reached a maximal intensity on day 7 through day 14. Induction of fibrosis was dose-dependent at the dose range of 5-40 ug, 7 days post-exposure. MWCNT elicited rapid and prominent infiltrations of neutrophils and macrophages alongside fibrosis implicating acute inflammation in the fibrotic response. At the molecular level, MWCNT induced elevated expression of proinflammatory cytokines TNFa, IL1a, IL1b, IL6, and CCL2 in lung tissues as well as the bronchoalveolar lavage fluid, in a dose- and time-dependent manner. MWCNT also increased the expression of fibrogenic growth factors TGF-B1 and PDGF-A in the lungs significantly. These findings underscore the interplay between acute inflammation and the early fibrotic response in the initiation and propagation of pulmonary fibrosis induced by MWCNT. [Description provided by NIOSH]
• Subjects:
  Animals Dust Fibrosis Irritants Laboratories Lung Lung Diseases Occupational Health Particulate Matter Pathology Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Animal Model Author Keywords: Nanotoxicity Cell-damage Cellular-reactions Cytokine Exposure-levels Fibrogenicity Fibrous-bodies Fibrous-dusts Growth Factor Inflammation Laboratory-animals Lung-disorders Lung-fibrosis Lung-tissue Lung Fibrosis Molecular-biology Nanotechnology Proteins Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiration Respiratory-irritants Respiratory-system-disorders Risk-factors

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• ISSN:
  0340-5761
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  89
• Issue:
  4
• NIOSHTIC Number:
  nn:20045574
• Citation:
  Arch Toxicol 2015 Apr; 89(4):621-633
• Contact Point Address:
  Jie Dong, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Mailstop 3014, Morgantown, WV 26505
• Email:
  qam1@cdc.gov
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Archives of Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8ac76d4155214c02b64571a780d57edeb22d8feb973edd2ec2079d4414e85f14e2ab1bebe0b0d4f6fea7ce2aab5df537bb53ddf8b6a15322f69acf3d2c6236c2
• Download URL:
  https://stacks.cdc.gov/view/cdc/200946/cdc_200946_DS1.pdf
• File Type:
  [PDF - 1.39 MB ]