Immunohistochemical localization of 3-nitrotyrosine in the nasal respiratory mucosa of patients with vasomotor rhinitis.

CONCLUSION: This study demonstrates that, in the nasal respiratory mucosa of patients with vasomotor rhinitis, oxidative stress following peroxynitrite formation is confined to the respiratory epithelium. This suggests that the role of peroxynitrite in vasomotor rhinitis differs from its role in other diseases of the respiratory tract. The results of this study also support the concept that different pathogenetic mechanisms are probably involved in vasomotor rhinitis. OBJECTIVE: Previous studies indicated that nitric oxide (NO) is involved in the pathogenesis of vasomotor rhinitis, strong expression of NO synthase being detected in the smooth muscle cells of the cavernous sinuses and in the respiratory epithelium. However, most adverse effects of high levels of NO originate from the reaction of NO with superoxide anions to form peroxynitrite. Therefore, in this study we evaluated the involvement of peroxynitrite in the pathogenesis of vasomotor rhinitis. MATERIAL AND METHODS: Sites of peroxynitrite formation were identified by immunolabelling for 3-nitrotyrosine (3NT), its footprint in tissues. Samples of nasal mucosa were obtained from vasomotor rhinitis patients and from control subjects who had undergone corrective surgery of the nasal septum. All samples were obtained by reduction of the inferior turbinate. RESULTS: Examination of specimens from vasomotor rhinitis patients revealed that 3NT is absent in epithelium with a normal appearance, cells of the subepithelial connective tissue, the glands and the blood vessels, including the cavernous sinuses. In contrast, intense 3NT immunolabelling was found in the disrupted respiratory epithelium. 3NT was not present in any of the specimens from control subjects.

Ultrastructural and ultracytochemical study of the human nasal respiratory epithelium in vasomotor rhinitis.

OBJECTIVES: Several pieces of evidence have suggested that nitric oxide (NO) fulfills important functions in the respiratory mucosa, under both normal and pathological conditions. This study was performed to investigate the role of NO in the nasal respiratory epithelium of patients affected by vasomotor rhinitis. The structure and ultrastructure of the epithelium were also examined. MATERIAL AND METHODS: The localization of NO synthase activity was determined by means of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase ultracytochemistry. Nasal mucosa was obtained from patients who had undergone surgical therapy for reduction of the inferior turbinate. RESULTS: Examination of hematoxylin-eosin-stained sections revealed that most of the nasal mucosa covering the surgical samples was characterized by severe epithelial damage. The ultrastructural study confirmed the light microscopic observations. Ciliary loss, absence of the intercellular junctions and distension of the intercellular spaces were found in the damaged epithelium. The basement membrane was frequently interrupted. Some epithelial cells were identified as basal cells. Other cells of the damaged epithelium were probably involuted ciliated and goblet cells. The ultracytochemical study showed that the basal cells were NADPH-diaphorase-negative in healthy subjects and strongly NADPH-diaphorase-positive in subjects with vasomotor rhinitis. CONCLUSIONS: It is suggested that NO has cytotoxic effects and causes inhibition of mitotic activity in the basal cells, leading to epithelial disruption and breakdown of the protective functions of the epithelium.