Resolution of Pulmonary Inflammation Induced by Carbon Nanotubes and Fullerenes in Mice: Role of Macrophage Polarization (Dataset)

Details

• Corporate Authors:
  National Institute for Occupational Safety and Health
• Description:
  Exposure to certain engineered nanomaterials (ENMs) causes chronic lesions like lung fibrosis and cancer as a result of unresolved inflammation. Elucidating how ENM-induced inflammation is resolved is necessary for better evaluation of the fibrogenic and tumorigenic potentials of ENMs. This study aimed to identify pro-resolving mechanisms by analyzing the inflammatory and fibrogenic responses to multi-walled carbon nanotubes (MWCNTs, Mitsui-7) and fullerenes (fullerene C60, C60F) in B6C3F1 mice. The findings reveal that MWCNTs at a low dose (40 microg/mouse) and C60F at a high dose (>480 mg/mouse) stimulated acute neutrophilic inflammation, which exhibited rapid initiation and extended resolution. The lesion in MWCNT-exposed mice progressed to fibrotic granulomas by day 28 post-exposure, whereas it remained as alveolar histiocytosis in C60F-exposed mice. The ENMs induced high levels of proinflammatory lipid mediators leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) with peaks at day 1, and high levels of specialized pro-resolving mediators resolvin D1 (RvD1) and E1 (RvE1) with peaks at day 7. Moreover, the ENMs induced time-dependent polarization of M1 macrophages and subsequently of M2 macrophages in the lung, accompanied by elevated levels of type 1 or type 2 cytokines, respectively. The M1 macrophages exhibited preferential induction of arachidonate 5-lipoxygenase activating protein (ALOX5AP), whereas M2 macrophages had a high-level expression of arachidonate 15-lipoxygenase (ALOX15). Polarization of macrophages in vitro differentially induced ALOX5AP in M1 macrophages and ALOX15 in M2 macrophages, both of which were further increased by MWCNTs. This study demonstrates that the neutrophilic inflammation induced by ENMs is actively resolved through the differential synthesis of proinflammatory and pro-resolving lipid mediators via distinct ALOX pathways in M1 or M2 macrophages in a time-dependent manner. Incomplete resolution of inflammation contributes to the chronic progression in mouse lungs exposed to persistent and high toxicity ENMs. [Description provided by NIOSH]
• Subjects:
  Blood Laboratories Lung Lung Diseases Macrophages Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Carbon Nanotubes Cellular Reactions CNT Fullerenes Immue Reaction Laboratory Animals Lung Disorders Nanomaterials Nanoparticles Pulmonary System Disorders
• DOI:
  https://doi.org/10.26616/NIOSHRD-1015-2020-0
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Dataset
• Genre:
  Research Dataset
• 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
• NIOSHTIC Number:
  nn:20060920
• Citation:
  Morgantown, WV: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Research Dataset RD-1015-2020-0, 2020 Sep; :dataset
• Contact Point Address:
  Qiang Ma, TMBB/HELD/NIOSH/CDC, 1000 Fredrick Lane, Morgantown WV 26508
• Email:
  qam1@cdc.gov
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Resolution of pulmonary inflammation induced by carbon nanotubes and fullerenes in mice: role of macrophage polarization
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c78d8ada0fccfa197dc08bd74ced66bc8c6850c729b6189e96fecbe331c1fcd73840facf7d786ff4191e528cfd5c87f9fbd7ba2474c30106ab95da1c5075490d
• Download URL:
  https://stacks.cdc.gov/view/cdc/224680/cdc_224680_DS1.pdf
• File Type:
  [PDF - 60.15 KB ]