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

Details

• Personal Author:
  Castranova, Vincent ; Zeidler P
• Description:
  Exposure of mice to lipopolysaccharide (LPS) plus interferon- gamma(IFN-gamma) increases nitric oxide (NO) production in the lung (Zeidler et al., 2003). The objective of the present study was to determine the role of inducible nitric oxide (iNOS)-induced NO in the pulmonary inflammatory response to LPS + IFN-gamma. Male mice (iNOS knockout vs. C57BL/6J wild type; 8-10 weeks old) were exposed to LPS (1.2 mg/kg) + IFN-gamma (5000 U/mouse) or to saline by pharyngeal aspiration, and pulmonary markers of damage and inflammation were compared at 24 and 72 hr post-exposure. The response at 24 hr post-exposure was marked by a decrease in total antioxidant capacity, increased alveolar macrophages, polymorphonuclear leukocytes, lactate dehydrogenase activity, albumin, tumor necrosis factor-a and macrophage inflammatory protein-2 in the acellular bronchoalveolar lavage fluid, and enhanced zymosan-stimulated chemiluminescence from alveolar macrophages to the same extent in both wild type and iNOS knockout mice. However, at 72 hr post-exposure the decline in antioxidant levels and the increase in markers of pulmonary damage and inflammation, and macrophage oxidant production were significantly greater in iNOS knockout vs. wild type mice. These data suggest that iNOS-derived NO plays an antiinflammatory role in modifying the pulmonary response to LPS + IFN-gamma. [Description provided by NIOSH]
• Subjects:
  Aluminum Silicates Lung Diseases Nitrous Oxide Occupational Health Respiratory Tract Diseases Safety Silicon Dioxide
• Keywords:
  Lung-disease Lung-disorders Nitrous-oxides Oxides Pulmonary-system-disorders Respiratory-system-disorders Silica-dusts Silicates
• ISSN:
  0891-5849
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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
• Volume:
  37
• NIOSHTIC Number:
  nn:20028028
• Citation:
  Free Radic Biol Med 2004 Jan; 37(Suppl 1):S49
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  False
• Source Full Name:
  Free Radical Biology and Medicine
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:297f72d812f460b26f6cab336dd8c965a52944d3da152a28180b8bd3501b007f51861941623e9965cbce8cc8633b66f42669fa5c211b5bb046a69b5a8548bace
• Download URL:
  https://stacks.cdc.gov/view/cdc/189738/cdc_189738_DS1.pdf
• File Type:
  [PDF - 91.82 KB ]