MyD88 mediates in vivo effector functions of alveolar macrophages in acute lung inflammatory responses to carbon nanotube exposure

Details

• Personal Author:
  Birch, M. Eileen ; Frank EA ; Yadav JS
• Description:
  Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wall CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation.We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca2+/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. [Description provided by NIOSH]
• Subjects:
  Aerosols Animals Hazardous Substances Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory System Risk Assessment Risk Factors Safety Toxicology Workplace

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• Keywords:
  Aerosol-particles Alveolar-cells Author Keywords: Nanotoxicology Carbon Nanotubes Cell-biology Cell-damage Cell-function Cellular-function Cellular-reactions Exposure-levels Fibrous-bodies Injuries Laboratory-animals Lung-disorders Lung-function Lung-irritants Macrophage Depletion Molecular Toxicology Nanotechnology Particle Toxicology Particulates Risk-factors Toxic-materials Toxins Work-environment Workers

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• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  322-329
• Volume:
  288
• Issue:
  3
• NIOSHTIC Number:
  nn:20046695
• Citation:
  Toxicol Appl Pharmacol 2015 Nov; 288(3):322-329
• Contact Point Address:
  Jagjit S. Yadav, University of Cincinnati College of Medicine, Department of Environmental Health, Kettering Laboratory Complex, 160 Panzeca Way, Cincinnati, OH 45267
• Email:
  Jagjit.Yadav@uc.edu
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e97b870f11b47c659387ebd509d86a79047bc61b3a6ff8ecba71368ecdadcbee4dae0b5306e01a4732992f5ed6630f625db78f5f375af9e2d38a4cbd7a6c4660
• Download URL:
  https://stacks.cdc.gov/view/cdc/202044/cdc_202044_DS1.pdf
• File Type:
  [PDF - 1.08 MB ]