Nasal polyp-derived superoxide anion: dose-dependent inhibition by nitric oxide and pathophysiological implications.
The epithelium of the paranasal sinuses produces nitric oxide (NO), which probably plays a major role in the nonspecific defense of these cavities through its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O2-*), but NO and O2-* inactivate reciprocally. The purpose of the present work was to evaluate the relationship between NO concentrations and nasal polyp production of O2-*. Polyp fragments from 24 patients were studied using histological examination and lucigenin-enhanced chemiluminescence (to assess O2-* production). The effect of various concentrations of exogenous NO on chemiluminescent signals was assessed. Basal and phorbol ester-stimulated O2-* production varied largely among patients, but both were highly related to eosinophilic infiltration. A slow releasing NO donor DETA NONOate (DETA/NO NOC-18) dose dependently inhibited lucigenin-enhanced chemiluminescence from phorbol ester-stimulated polyp fragments, with an EC50 of 1.5 mM. The NO concentration in normal maxillary sinus was estimated about 10 ppm (i.e., 0.5 microM in aqueous phase) (Lundberg, et al. Nature Med 1995;1:370). Calculations revealed that the DETA NONOate 0.75 mM and 1.5 mM generate steady-state concentrations of NO of 0.5 microM and 2.5 microM, respectively. In conclusion, the NO concentration present in paranasal sinuses appears to partially suppress (approximately 20-40%) O2-* production from polyp eosinophils. Conversely, phagocytic-derived O2-* could contribute to decrease sinus NO concentration, further altering this natural local defense. Together, these events could participate in chronic inflammation and contribute to the pathophysiology of nasal polyps.
Pasto
M
M
Service d'Exploration Fonctionnelle Respiratoire et INSERM U397, Rangueil, France.
Serrano
E
E
Urocoste
E
E
Barbacanne
M A
MA
Guissani
A
A
Didier
A
A
Delisle
M B
MB
Rami
J
J
Arnal
J F
JF
D000166:Acridines; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D000166:Acridines; D013481:Superoxides; C033472:10,10'-dimethyl-9,9'-biacridinium; D009569:Nitric Oxide