NADPH Oxidase Regulates Neutrophils and Fibrosis in C57BL/6 Mice Exposed to Carbon Nanotubes

Details

• Personal Author:
  Castranova, Vincent ; Kisin ER ; Kommineni C ; Murray AR ; Shvedova AA ; Castranova, Vincent ; Kisin ER ; Kommineni C ; Murray AR ; Shvedova AA
• Description:
  Single-walled carbon nanotubes (SWCNT) have been introduced into a large number of new technologies and consumer products. The combination of their exceptional features with very broad applications raised concerns regarding their potential health effects. The prime target for SWCNT toxicity is believed to be the lung where exposure may occur through inhalation, particularly in occupational settings. Our previous work has demonstrated that SWCNT cause robust inflammatory responses in rodents with very early termination of the acute phase and rapid onset of chronic fibrosis. Timely elimination of polymorphonuclear neutrophils (PMNs) through apoptosis and their subsequent clearance by macrophages is a necessary stage in the resolution of pulmonary inflammation whereby NADPH oxidase contributes to control of apoptotic cell death and clearance of PMNs. Thus, we hypothesized that NADPH oxidase may be an important regulator of the transition from the acute inflammation to the chronic fibrotic stage in response to SWCNT. To experimentally address the hypothesis, we employed NADPH oxidase-deficient mice which lack the gp91phox sub-unit of the enzymatic complex. We found that NADPH oxidase null mice responded to SWCNT exposure with a marked accumulation of PMNs and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-beta, and significantly lower levels of collagen deposition, as compared to C57BL/6 control mice. These results demonstrate a role for NADPH oxidase-derived reactive oxygen species in determining course of pulmonary response to SWCNT. [Description provided by NIOSH]
• Subjects:
  Biological Factors Blood Cytology Dust Environmental Monitoring Fibrosis Irritants Laboratories Lung Lung Diseases Microbiology Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Workplace

  More +
• Keywords:
  Biological-effects Biological-factors Blood-cells Cell-biology Cell-damage Cellular-reactions Exposure-assessment Exposure-levels Exposure-methods Fibrogenesis Fibrogenicity Fibrous-bodies Fibrous-dusts Inhalation-studies Laboratory-animals Lung-cells Lung-disorders Lung-irritants Microscopic-analysis Microscopy Nanotechnology Oxidation-reduction-reactions Oxidative-processes Particle-aerodynamics Particulate-dust Particulates Quantitative-analysis Respiratory-irritants Respiratory-system-disorders Statistical-analysis Work-environment Workplace-studies

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035295
• Citation:
  Toxicologist 2009 Mar; 108(1):410
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4776a852222a9cbff368ef4d19ba588a91b6bcce5074a433ca108d32bc7c1b8ace248547c8ca291fad9edffd2591fc29bc56c791ff9701f841edbdbbd559deb2
• Download URL:
  https://stacks.cdc.gov/view/cdc/187203/cdc_187203_DS1.pdf
• File Type:
  [PDF - 1.58 MB ]