EXPRESSION AND LOCALIZATION OF THE INDUCIBLE ISOFORM OF NITRIC-OXIDE SYNTHASE IN NASAL POLYP EPITHELIUM

Background The pathogenesis of nasal polyp disease is poorly understoo d. 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 be en identified in humans, with the inducible isoform (iNOS) generally e xpressed in the setting of inflammation.Objective The aim of this stud y was to detect and localize iNOS expression in nasal polyp. tissue, a nd 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 undergoi ng elective nasal turbinectomy (n = 5) or nasal polypectomy (n = 5). i NOS mRNA expression was determined by semi-quantitative reverse transc ription-polymerase chain reaction (RT-PCR) followed by Southern blot a nalysis and localised by in situ hybridization. Densitometric data wer e analysed using Student's unpaired t-test. Adjacent sections were als o examined for iNOS protein expression by immunohistochemistry. Result s Semi-quantitative RT-PCR/Southern analysis of RNA obtained from the 10 surgical specimens demonstrated that iNOS mRNA expression was signi ficantly increased in the five nasal polyps (P < 0.05). Irt situ hybri dization studies revealed strong iNOS mRNA signal localized to the res piratory epithelium of nasal polyps, but not nasal turbinates. This pa ttern was confirmed by immunohistochemistry. Localization to inflammat ory 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 pathoge nesis of nasal disease, and suggest a potential role for NO in the for mation of nasal polyps.