Expression and localization of the inducible isoform of nitric oxide synthase in nasal polyp epithelium.
BACKGROUND
The pathogenesis of nasal polyp disease is poorly understood. Recent evidence has suggested that nitric oxide (NO), an endogenous soluble gas vasodilator and inflammatory mediator, may be synthesised within the nasal cavity. Three nitric oxide synthase isoforms have been identified in humans, with the inducible isoform (iNOS) generally expressed in the setting of inflammation.


OBJECTIVE
The aim of this study was to detect and localize iNOS expression in nasal polyp tissue, and compare these findings with normal nasal turbinate tissue.


METHODS
We examined the expression and localisation of inducible nitric oxide synthase (iNOS) in human nasal airway specimens from patients undergoing elective nasal turbinectomy (n = 5) or nasal polypectomy (n = 5). iNOS mRNA expression was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis and localised by in situ hybridization. Densitometric data were analysed using Student's unpaired t-test. Adjacent sections were also examined for iNOS protein expression by immunohistochemistry.


RESULTS
Semi-quantitative RT-PCR/Southern analysis of RNA obtained from the 10 surgical specimens demonstrated that iNOS mRNA expression was significantly increased in the five nasal polyps (P < 0.05). In situ hybridization studies revealed strong iNOS mRNA signal localized to the respiratory epithelium of nasal polyps, but not nasal turbinates. This pattern was confirmed by immunohistochemistry. Localization to inflammatory cells or other subepithelial structures was not seen.


CONCLUSIONS
We conclude that iNOS expression is upregulated in nasal polyp disease, and is localized to the polyp epithelial layer. These data reinforce the concept that the epithelial layer may be important in the pathogenesis of nasal disease, and suggest a potential role for NO in the formation of nasal polyps.
Watkins
D N
DN
The University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
Lewis
R H
RH
Basclain
K A
KA
Fisher
P H
PH
Peroni
D J
DJ
Garlepp
M J
MJ
Thompson
P J
PJ
D004848:Epithelium / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D009298:Nasal Polyps / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D007527:Isoenzymes; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II