Dual acute proinflammatory and antifibrotic pulmonary effects of short palate, lung, and nasal epithelium clone-1 after exposure to carbon nanotubes

Details

• Personal Author:
  Di YP ; Gao SL ; Kagan VE ; Kisin ER ; Shurin MR ; Shvedova A ; Stanley S ; Tkach AV ; Yanamala N
• Description:
  Carbon nanotubes (CNTs; allotropes of carbon with a cylindrical nanostructure) have emerged as one of the most commonly used types of nanomaterials, with numerous applications in industry and biomedicine. However, the inhalation of CNTs has been shown to elicit pulmonary toxicity, accompanied by a robust inflammatory response with an early-onset fibrotic phase. Epithelial host-defense proteins represent an important component of the pulmonary innate immune response to foreign inhalants such as particles and bacteria. The short palate, lung, and nasal epithelium clone-1 (SPLUNC1) protein, a member of the bactericidal/permeability-increasing-fold (BPIF)-containing protein family, is a 25-kD secretory protein that is expressed in nasal, oropharyngeal, and lung epithelia, and has been shown to have multiple functions, including antimicrobial and chemotactic activities, as well as surfactant properties. This study sought to assess the importance of SPLUNC1-mediated pulmonary responses in airway epithelial secretions, and to explore the biological relevance of SPLUNC1 to inhaled particles in a single-walled carbon nanotube (SWCNT) model. Using Scgb1a1-hSPLUNC1 transgenic mice, we observed that SPLUNC1 significantly modified host inflammatory responses by increasing leukocyte recruitment and enhancing phagocytic activity. Furthermore, we found that transgenic mice were more susceptible to SWCNT exposure at the acute phase, but showed resistance against lung fibrogenesis through pathological changes in the long term. The binding of SPLUNC1 also attenuated SWCNT-induced TNF-alpha secretion by RAW 264.7 macrophages. Taken together, our data indicate that SPLUNC1 is an important component of mucosal innate immune defense against pulmonary inhaled particles. [Description provided by NIOSH]
• Subjects:
  Animals Energy Metabolism Environmental Monitoring Immune System Inhalation Exposure Laboratories Lung Lung Diseases Occupational Health Particulate Matter Pathology Respiratory System Respiratory Tract Diseases Safety Surface-Active Agents

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• Keywords:
  Airway-resistance Alveolar-cells Animal-studies Antibacterial-agents Author Keywords: SPLUNC1 Bactericides BPIFA1 Carbon Nanotube Exposure-assessment Fibrogenesis Fibrosis Fibrous-bodies Glycoproteins Host-resistance Immune-reaction Immunology Inflammation Inhalants Laboratory-animals Laboratory-testing Leukocytes Lung-cells Lung-disorders Lung-fibrosis Metabolism Mucous-membranes Nanotechnology Phagocytes Proteins Pulmonary-system-disorders Respiratory-system-disorders Surfactants

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• ISSN:
  1044-1549
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; 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:
  49
• Issue:
  5
• NIOSHTIC Number:
  nn:20043566
• Citation:
  Am J Respir Cell Mol Biol 2013 Nov; 49(5):759-767
• Contact Point Address:
  Y. Peter Di, Ph.D., Department of Environmental and Occupational Health, University of Pittsburgh, 100 Technology Drive, Suite 322, Bridgeside Point, Pittsburgh, PA 15219
• Email:
  peterdi@pitt.edu
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  American Journal of Respiratory Cell and Molecular Biology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dd0179926d3ae25aa65d573b2cbe5f388b83fcb4d3d2830e995a736c2ca240ca699d98c8eb348a030e65e548cdb1affb7f590717e1a762e24dfde566413d27b8
• Download URL:
  https://stacks.cdc.gov/view/cdc/195439/cdc_195439_DS1.pdf
• File Type:
  [PDF - 1.61 MB ]