Role of Inducible Nitric Oxide-Derived Nitric Oxide in Silica-Induced Pulmonary Inflammation and Injury

Details

• Personal Author:
  Castranova, Vincent ; Hubbs, Ann F. ; Zeidler PC
• Description:
  Our lab has demonstrated previously that exposure of rats to silica resulted in induction of inducible nitric oxide synthase (iNOS) in alveolar macrophages (AM) and alveolar type II epithelial cells (TII). The production of nitric oxide (NO) by these pneumocytes and resultant NO-dependent damage (nitrotyrosine residues) have been related temporally and anatomically with silica-induced inflammation and granuloma formation (Am J Physiol Lung Cell Mol Physiol 283:L485, 2002). The objective of the present study was to determine if these associations represent a causal role for NO in silica-induced lung disease. To address this question, the sub-chronic response of C57BL/6J wild type (WT) mice and iNOS knockout (KO) mice to aspiration of silica (40 mg/kg) was compared 42 days post-exposure. Exposure of WT mice to silica was marked by the following sub-chronic responses: pulmonary damage (increased LDH and albumin levels in lung lavage fluid, and increased lung weight), inflammation (increased lung lavage polymorphonuclear leukocytes, TNF-alpha, MIP-2 and TGF-beta, and histological evidence of alveolitis and lipoproteinosis), oxidant stress (increased zymosan-stimulated chemiluminescence from AM, and decreased total antioxidant levels in lung lavage fluid), and fibrosis (increased lung hydroxyproline levels). Absence of the iNOS gene in KO mice resulted in a significant decrease in markers of pulmonary damage, inflammation, oxidant stress and fibrosis 42 days after silica exposure. These data indicate that NO production plays a causal role in the progression of silica-induced lung disease. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Environmental Exposure Fibrosis Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide

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• Keywords:
  Animal Studies Exposure Levels Injuries Laboratory Animals Lung Disease Lung Disorders Nitrous Oxides Oxides Pulmonary System Disorders Respiratory System Disorders Silica Dusts Silicates

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• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• 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
• Pages in Document:
  143-144
• Volume:
  78
• NIOSHTIC Number:
  nn:20025065
• Citation:
  Toxicologist 2004 Mar; 78(S-1):143-144
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9) ; Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland
• Supplement:
  S-1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:08ab9ba1c919f1d463bb86c252fd6d637cd73066309167a54e877d64b9979df8755bad9abf1269eec660bab6b1c4cfb6021e4d50df4e23134cb4c1994e7fdafb
• Download URL:
  https://stacks.cdc.gov/view/cdc/196570/cdc_196570_DS1.pdf
• File Type:
  [PDF - 98.39 KB ]