Am. J. Respir. Crit. Care Med.,
Volume 163, Number 1, January 2001, 145-151
Nasal Polyp-Derived Superoxide Anion
Dose-Dependent Inhibition by Nitric Oxide and
Pathophysiological Implications
MERITXELL
PASTO,
ELIE
SERRANO,
EMANUELLE
UROCOSTE,
MARIE-ALINE
BARBACANNE,
ANNIE
GUISSANI,
ALAIN
DIDIER,
MARIE-BERNADETTE
DELISLE,
JACQUES
RAMI,
and
JEAN-FRANÇOIS
ARNAL
Services d'Exploration Fonctionnelle Respiratoire et INSERM U397, de Pneumologie et d'Allergologie, d'ORL, et d'Anatomopathologie,
Rangueil, France; Laboratoire de Synthèse, Physico-Chimie et Radiobiologie, Université Paul Sabatier, Toulouse Cedex, France, and
Institut Curie, Bat 112, INSERM U350, Centre Universitaire, Orsay, France
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 µM 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 µM and 2.5 µM,
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.
