Nitric oxide as a noninvasive biomarker of lipopolysaccharide-induced airway inflammation: possible role in lung neutrophilia

The Journal of Pharmacology and Experimental Therapeutics
Kerryn McCluskieMaria G Belvisi

Abstract

Lipopolysaccharide (LPS) is known to generate nitric oxide (NO) in the airway through the activation of nitric-oxide synthase (NOS). The functional consequences of this on the inflammatory response are not clear, with conflicting data published. In the clinic, exhaled NO (ex-NO) is used as a noninvasive biomarker to assess the extent of airway inflammation. It is proposed that monitoring levels of ex-NO could be a useful guide to determining the effectiveness of disease modifying therapies. The aim was, using pharmacological tools, to determine the role of NO in an aerosolized LPS-driven animal model of airway inflammation by assessment of ex-NO, neutrophilia, and inflammatory biomarkers, using a nonselective NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME), and a selective inducible NOS (iNOS) inhibitor, N-3 (aminomethyl)benzyl)acetamidine (1400W). Real-time mRNA analysis of the lung tissue indicated an increased gene expression of iNOS following LPS challenge with minimal impact on constitutive NOS isoforms. LPS induced an increase in ex-NO, which appeared to correlate with the increase in iNOS gene expression and airway neutrophilia. Treatment with l-NAME and 1400W resulted in comparable reductions in ex-NO, a redu...Continue Reading

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Citations

May 20, 2006·American Journal of Respiratory Cell and Molecular Biology·Carla M PradoIolanda F L C Tibério
Jan 1, 2011·ISRN Allergy·Carla M PradoIolanda F L C Tibério
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Jul 25, 2006·The Journal of Pharmacology and Experimental Therapeutics·Kerryn McCluskieG Roger Thomas
May 13, 2006·The Journal of Pharmacology and Experimental Therapeutics·Mark A BirrellMaria G Belvisi
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