Role of Inducible Nitric Oxide Synthase-Derived Nitric Oxide in Lipopolysaccharide plus Interferon-Gamma-Induced Pulmonary Inflammation

Details

• Personal Author:
  Castranova, Vincent ; Millecchia LM ; Zeidler PC
• Description:
  Exposure of mice to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) increases nitric oxide (NO) production, which is proposed to play a role in the resulting pulmonary damage and inflammation. To determine the role of inducible nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT) mice to aspirated LPS + IFN-gamma were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-gamma (5000 U/mouse) or saline. At 24 or 72 h postexposure, lungs were lavaged with saline and the acellular fluid from the first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-alpha (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN-gamma were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-alpha, and MIP-2, and enhanced AM-CL to the same extent in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however, significant differences were found between WT and iNOS KO mice. iNOS KO mice demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs, LDH, albumin, TNF-alpha, and MIP-2, and an enhanced AM-CL compared to the WT. These data suggest that the role of iNOS-derived NO in the pulmonary response to LPS + IFN-gamma is anti-inflammatory, and this becomes evident over time. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Animals Fibrosis Laboratories Lung Diseases Nitrous Oxide Occupational Health Respiratory Tract Diseases Safety Silicon Dioxide
• 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:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• 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
• Pages in Document:
  45-54
• Volume:
  195
• Issue:
  1
• NIOSHTIC Number:
  nn:20024598
• Citation:
  Toxicol Appl Pharmacol 2004 Feb; 195(1):45-54
• Contact Point Address:
  Health Effects Laboratory Division, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, M/S 2015, Morgantown, WV 26505
• Email:
  vic1@cdc.gov
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0e23e0c583132326c6a7d33e7f034cc5accd6a30d94a172014b985a55fa1e084f660f48a8c6cb44449717a980e29a7255cce100ad41a2ff607f5b458f43c131e
• Download URL:
  https://stacks.cdc.gov/view/cdc/196332/cdc_196332_DS1.pdf
• File Type:
  [PDF - 287.03 KB ]