Investigation of the role of osteopontin in pulmonary granuloma formation and fibrosis following carbon nanotube exposure

Details

• Personal Author:
  Erdely A ; Eye T ; Liston A ; Mercer RR ; Salmen R ; Smith K ; Zeidler-Erdely PC
• Description:
  Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) is known to induce granuloma formation with associated fibrosis. Granuloma formation following a pulmonary exposure is dependent on osteopontin (OPN) production by regulating macrophage accumulation. Levels of OPN are increased in silicosis, tuberculosis, and asbestos-related pathologies and circulating levels may serve to elucidate disease progression. In this study, we investigated the role of OPN in the fibrotic and granulomatous response following MWCNT exposure. Wild-type (WT) or OPN-deficient (OPN-/-) mice were exposed by oropharyngeal aspiration to vehicle (DM; 0.6 mg/ml mouse serum albumin and 0.01 mg/ml DPPC) or 40 microg of MWCNT, a dose known to induce granulomas, and sacrificed 1, 7, and 28 d post-exposure. Pulmonary OPN relative mRNA expression (peaked at 7 d) and protein levels were induced in wild-type mice following MWCNT exposure. No detectable levels of OPN were found in the OPN-/- mice, verifying the knockout model. With OPN deficiency, microgranuloma incidence (6/6 WT; 1/4 OPN-/-) and severity (1.50 +/- 0.34 WT vs 0.25 +/- 0.25 OPN-/-) was reduced 28 d post-exposure. Scoring of perivascular and peribronchial lymphoid infiltrates was also reduced (1.83 +/- 0.17 WT vs 0.75 +/- 0.25 OPN-/-). General fibrosis scored from Trichome-stained sections showed 100 % incidence in all exposed mice with no difference in severity (1.80 +/- 0.20 WT vs 1.75 +/- 0.25 OPN-/-). Alveolar fibrosis, measured as alveolar wall thickness (microm), from Picro-Sirius Red staining was increased due to exposure but not affected by deficiency of OPN (0.93 +/- 0.05 WT/DM; 1.06 +/- 0.05 OPN-/-/DM; 1.62 +/- 0.07 WT/MWCNT; 1.50 +/- 0.15 OPN-/-/MWCNT). Pulmonary cytotoxicity, inflammatory cell influx, and relative mRNA expression of genes related to macrophage function and recruitment (Ccl2, Ccl22, and Arg1) were increased as a result of MWCNT exposure but not affected by OPN deficiency. In conclusion, OPN deficiency prevented the development of granulomas but did not have a major influence on general inflammatory parameters or the development of fibrosis. [Description provided by NIOSH]
• Subjects:
  Albumins Blood Cytotoxins Fibrosis Immune System Laboratories Lung Lung Diseases Macrophages Musculoskeletal System Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Albumin Alveolar Cells Blood Serum Carbon Nanotubes Cellular Effects Cellular Reactions Cytotoxicity Dispersion Exposure Assessment Gene Expression Immune Reaction Immune System Laboratory Animals Laboratory Testing Lung Fibrosis Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotoxicology Nanotubes Osteogenesis Proteins Pulmonary Effects Tissue Distribution

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; 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:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049479
• Citation:
  Toxicologist 2017 Mar; 156(1):404
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Osteopontin (rat clone λROP11 protein moiety) (CAS RN 106441-73-0)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cfd751a9a39f20b9b04d6515c6dec927ec9102d7ec099ea93a5480413f66c1c26674b536a42c86ca853baf43ac5edcf895c90aa827659dd041e53ee5eeae22fd
• Download URL:
  https://stacks.cdc.gov/view/cdc/203921/cdc_203921_DS1.pdf
• File Type:
  [PDF - 945.09 KB ]