Document Detail

In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS.
MedLine Citation:
PMID:  12409313     Owner:  NLM     Status:  MEDLINE    
Intratracheal instillation of lipopolysaccharide (LPS) activates alveolar macrophages and infiltration of neutrophils, causing lung injury/acute respiratory distress syndrome. Free radicals are a special focus as the final causative molecules in the pathogenesis of lung injury caused by LPS. Although in vitro investigation has demonstrated radical generation after exposure of cells to LPS, in vivo evidence is lacking. Using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), we investigated in vivo free radical production by rats treated with intratracheal instillation of LPS. ESR spectroscopy of lipid extract from lungs exposed to LPS for 6 h gave a spectrum consistent with that of a POBN/carbon-centered radical adduct (aN=14.94+/-0.07 G and abetaH=2.42+/-0.06 G) tentatively assigned as a product of lipid peroxidation. To further investigate the mechanism of LPS-initiated free radical generation, rats were pretreated with the phagocytic toxicant GdCl3, which significantly decreased the production of radical adducts with a corresponding decrease in neutrophil infiltration. NADPH oxidase knockout mice completely blocked phagocyte-mediated, ESR-detectable radical production in this model of acute lung injury. Rats treated intratracheally with LPS generate lipid-derived free radicals via activation of NADPH oxidase.
Keizo Sato; Maria B Kadiiska; Andrew J Ghio; Jean Corbett; Yang C Fann; Steven M Holland; Ronald G Thurman; Ronald P Mason
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  16     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-31     Completed Date:  2002-12-16     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1713-20     Citation Subset:  IM    
Free Radical Metabolite Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
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MeSH Terms
Bronchoalveolar Lavage Fluid / chemistry,  cytology
Disease Models, Animal
Electron Spin Resonance Spectroscopy
Free Radicals / metabolism*
Gadolinium / pharmacology
Infant, Newborn
Lipid Metabolism*
Lipopolysaccharides / administration & dosage*,  toxicity
Lung / drug effects*,  metabolism,  pathology
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
NADPH Oxidase / genetics,  metabolism*
Nitrogen Oxides / administration & dosage,  toxicity
Phagocytes / cytology,  drug effects
Proteins / drug effects,  metabolism
Rats, Sprague-Dawley
Respiratory Distress Syndrome, Newborn / chemically induced,  metabolism,  pathology
Reg. No./Substance:
0/Free Radicals; 0/Lipopolysaccharides; 0/Nitrogen Oxides; 0/Proteins; 0/Pyridines; 0/alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; 10138-52-0/gadolinium chloride; 7440-54-2/Gadolinium; EC Oxidase

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