RGD Reference Report - Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats. - Rat Genome Database

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Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats.

Authors: Setoguchi, K  Takeya, M  Akaike, T  Suga, M  Hattori, R  Maeda, H  Ando, M  Takahashi, K 
Citation: Setoguchi K, etal., Am J Pathol. 1996 Dec;149(6):2005-22.
RGD ID: 4891457
Pubmed: PMID:8952535   (View Abstract at PubMed)
PMCID: PMC1865352   (View Article at PubMed Central)

Two types of pulmonary granulomatosis were produced in rats by intratracheal instillation of zymosan or silica. In both models, immunostaining with anti-rat monoclonal antibody for inducible nitric oxide synthase (iNOS), ANOS11, showed that the intensity of iNOS immunoreactivity in the inflammatory lesions peaked at 3 days and declined thereafter. Immunohistochemical double staining and in situ hybridization demonstrated the expression of iNOS in neutrophils, monocyte-derived macrophages, and bronchiolar epithelial cells in the pulmonary lesions. Electron spin resonance spectroscopy revealed the production of an excessive amount of nitric oxide (NO) in the pulmonary lesions. Immunostaining with a polyclonal antibody against nitrotyrosine indicated the formation of nitrotyrosine residues in the granulomatous lesions, particularly in the periphery of the lesions, providing indirect evidence for the generation of peroxynitrite anion in the zymosan- or silica-instilled lungs. Administration of N omega-nitro-L-arginine methyl ester or S-methylisothiourea sulfate, which significantly suppressed NO production, resulted in marked reduction of monocyte/macrophage infiltration as well as in inhibition of induction of monocyte chemoattractant protein-1 in the lesions. These data indicate that NO and its more reactive product peroxynitrite anion may be important mediators of granuloma formation in the lung.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung disease  ISONos2 (Rattus norvegicus)4891457; 4891457associated with Granuloma and protein:increased expression:lungRGD 
lung disease  IEP 4891457associated with Granuloma and protein:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos2  (nitric oxide synthase 2)

Genes (Mus musculus)
Nos2  (nitric oxide synthase 2, inducible)

Genes (Homo sapiens)
NOS2  (nitric oxide synthase 2)


Additional Information