Nasal polyp-derived superoxide anion - Dose-dependent inhibition by nitricoxide and pathophysiological implications

The epithelium of the paranasal sinuses produces nitric oxide (NO), which p robably plays a major role in the nonspecific defense of these cavities thr ough its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O-2(-.) ), but NO and O-2(-.) inactivate reciprocally. The purpose of the present w ork was to evaluate the relationship between NO concentrations and nasal po lyp production of O-2(-.). Polyp fragments from 24 patients were studied us ing histotogical examination and lucigenin-enhanced chemiluminescence (to a ssess O-2(-.) production). The effect of various concentrations of exogenou s NO on chemiluminescent signals was assessed. Basal and phorbol ester-stim ulated O-2(-.) production varied largely among patients, but both were high ly related to eosinophilic infiltration. A slow releasing NO donor DETA NON Oate (DETA/NO NOC-18) dose dependently inhibited lucigenin-enhanced chemilu minescence from phorbol ester-stimulated polyp fragments, with an EC50 of 1 .5 mM. The NO concentration in normal maxillary sinus was estimated about 1 0 ppm (i.e., 0.5 muM in aqueous phase) (Lundberg, et al. Nature Med 1995;1: 370), Calculations revealed that the DETA NONOate 0.75 mM and 1.5 mM genera te steady-state concentrations of NO of 0.5 muM and 2.5 muM, respectively. In conclusion, the NO concentration present in paranasal sinuses appears to partially suppress (approximately 20-40%) O-2(-.) production from polyp eo sinophils. Conversely, phagocytic-derived O-2(-.) could contribute to decre ase sinus NO concentration, further altering this natural local defense. To gether, these events could participate in chronic inflammation and contribu te to the pathophysiology of nasal polyps.