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Title: Interactive effects of cerium oxide and diesel exhaust nanoparticles on inducing pulmonary fibrosis

Cerium compounds have been used as a fuel-borne catalyst to lower the generation of diesel exhaust particles (DEPs), but are emitted as cerium oxide nanoparticles (CeO{sub 2}) along with DEP in the diesel exhaust. The present study investigates the effects of the combined exposure to DEP and CeO{sub 2} on the pulmonary system in a rat model. Specific pathogen-free male Sprague–Dawley rats were exposed to CeO{sub 2} and/or DEP via a single intratracheal instillation and were sacrificed at various time points post-exposure. This investigation demonstrated that CeO{sub 2} induces a sustained inflammatory response, whereas DEP elicits a switch of the pulmonary immune response from Th1 to Th2. Both CeO{sub 2} and DEP activated AM and lymphocyte secretion of the proinflammatory cytokines IL-12 and IFN-γ, respectively. However, only DEP enhanced the anti-inflammatory cytokine IL-10 production in response to ex vivo LPS or Concanavalin A challenge that was not affected by the presence of CeO{sub 2}, suggesting that DEP suppresses host defense capability by inducing the Th2 immunity. The micrographs of lymph nodes show that the particle clumps in DEP + CeO{sub 2} were significantly larger than CeO{sub 2} or DEP, exhibiting dense clumps continuous throughout the lymph nodes. Morphometric analysis demonstratesmore » that the localization of collagen in the lung tissue after DEP + CeO{sub 2} reflects the combination of DEP-exposure plus CeO{sub 2}-exposure. At 4 weeks post-exposure, the histological features demonstrated that CeO{sub 2} induced lung phospholipidosis and fibrosis. DEP induced lung granulomas that were not significantly affected by the presence of CeO{sub 2} in the combined exposure. Using CeO{sub 2} as diesel fuel catalyst may cause health concerns. - Highlights: • DEP induced acute lung inflammation and switched immune response from Th1 to Th2. • DEP induced lung granulomas were not affected by the presence of CeO{sub 2}. • CeO{sub 2} induced sustained lung inflammation, phospholipidosis, and fibrosis. • After the combined exposure, CeO{sub 2} and DEP are co-localized in the lung tissues. • CeO{sub 2} + DEP induced lung inflammation, phospholipidosis, granulomas, and fibrosis.« less
Authors:
 [1] ; ; ; ;  [1] ;  [2] ;  [1]
  1. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States)
  2. School of Pharmacy, West Virginia University, Morgantown, WV 26506 (United States)
Publication Date:
OSTI Identifier:
22439785
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 278; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARGINASE; CATALYSTS; CERIUM OXIDES; COLLAGEN; CONCANAVALIN A; DIESEL FUELS; FIBROSIS; GRANULOMAS; INFLAMMATION; LUNGS; LYMPH NODES; LYMPHOCYTES; LYMPHOKINES; MACROPHAGES; NANOPARTICLES; PATHOGENS; PHOSPHOLIPIDS; RATS; SECRETION; TRANSMISSION ELECTRON MICROSCOPY