3-nitrotyrosine and Nasal-Polyps

Several works have reported that nitric oxide and free oxygen radicals are up-regulated in nasal polyposis. This study aimed to assess the distribution of peroxynitrite in nasal polyps from nonatopic patients. Occurrence of peroxynitrite also was analyzed in relation with eosinophil infiltration and epithelial alterations.. Hematoxylin and eosin staining was used for histologic study. Peroxynitrite was assessed by 3-nitrotyrosine immunohistochemistry. Quantitative evaluation was done by measuring the total number of eosinophils, the number of 3-nitrotyrosine-positive eosinophils, and the extension of the various epithelial alterations.. Hematoxylin and eosin staining showed that the nasal polyp epithelium is characterized by progressive disruption or squamous metaplasia. In both cases, infiltrating eosinophils were found in the epithelium and lamina propria. The regions featuring epithelial disruption exhibited 3-nitrotyrosine immunostaining in eosinophils and epithelial cells; hematoxylin-and-eosin - stained eosinophils and 3-nitrotyrosine - positive eosinophils showed conspicuous variations in number. Within the regions featuring squamous metaplasia, 3-nitrotyrosine-positive eosinophils were rarely found, and the epithelium exhibited 3-nitrotyrosine only in the superficial cells. In these regions, hematoxylin-eosin - stained eosinophils showed slight variations in number.. Peroxynitrite plays a pivotal role in the pathophysiology of nasal polyps. In fact, strong expression of peroxynitrite is associated with epithelial disruption, while poor expression of peroxynitrite is associated with squamous metaplasia. Peroxynitrite could influence afflux of eosinophils in the nasal mucosa; moreover, the total number of eosinophils is not critical in generating alterations of nasal polyp mucosa.

Topics: Adult; Epithelium; Female; Free Radicals; Gene Expression Regulation; Humans; Immunohistochemistry; Male; Metaplasia; Models, Biological; Nasal Mucosa; Nasal Polyps; Oxygen; Peroxynitrous Acid; Tyrosine

Nasal polyposis is characterized by impaired regulation of nasal tissue growth and is associated with chronic inflammation, sinus infections, and low levels of nitric oxide (NO). Based on its critical role in mediating cell growth and antimicrobial function, decrease of NO levels has been implicated in the pathogenesis of nasal polyposis.. We sought to evaluate mechanisms for the low NO level in polyposis, including factors regulating NO synthase (NOS) expression and activity and NO consumptive processes in nasal epithelial cells and nasal lavage fluid.. Eighteen patients with nasal polyposis and 8 healthy control subjects were studied. Nasal brushings, nasal lavage fluid, and nasal biopsy specimens were collected and analyzed.. NO metabolite levels (nitrite and nitrate) in nasal lavage fluid from patients with polyps were less than those in control subjects, but activation of signal transduction and inducer of transcription 1, which regulates inducible NOS gene expression and protein expression, was present at higher levels in polyp than in healthy control tissue. Levels of arginine, methylarginine, and endogenous NOS inhibitors were similar between polyp and control tissue. In contrast, superoxide dismutase activity of polyp tissues was lower than that seen in control tissue and associated with increased nitrotyrosine, a biomarker of oxidant consumptive products of NO.. Taken together, these data suggest that the nasal polyp environment is characterized by abnormalities in NO metabolism that might predispose to altered regulation of tissue growth and infection.. Identification of NO metabolic abnormalities might lead to novel treatments for sinonasal polyposis targeted against the pathways identified within this study.

Topics: Adult; Enzyme Inhibitors; Female; Humans; Male; Nasal Polyps; Nitric Oxide; Nitric Oxide Synthase Type II; omega-N-Methylarginine; Oxidation-Reduction; Oxygen Consumption; Polymorphism, Single Nucleotide; Signal Transduction; STAT1 Transcription Factor; Substrate Specificity; Superoxide Dismutase; Tyrosine

To investigate whether formation of nitrotyrosine in the nasal polyps of atopic patients occurs.. A nonrandomized, retrospective, controlled qualitative and quantitative study.. Nasal polyp tissue samples were acquired from 12 atopic patients. Control fragments of nasal mucosa were taken from 10 patients undergoing corrective surgery of the nasal septum. For routine histologic examinations, hematoxylin-eosin staining was used. Low-magnification microscopy was designed to yield pathologic characteristics and high magnification to quantify the number of eosinophils in the subepithelial connective tissue. Presence of nitrotyrosine was assessed by immunohistochemical method.. Hematoxylin-eosin staining revealed presence of numerous eosinophils in the epithelium and in the subepithelial connective tissue. All polyps were characterized by epithelial damage. Nitrotyrosine was present in the eosinophils, in the ciliated cell, and in cells of the damaged epithelium. Goblet cells, glands, and vessels were found to be negative. No significant differences concerning the localization of nitrotyrosine were recognized among the examined nasal polyps.. Nitrotyrosine immunohistochemical staining in nasal-polyp tissues suggested the existence of progressive epithelium injury caused by peroxynitrite. Consequences of peroxynitrite formation in eosinophils remain to be precisely established. The lack of nitrotyrosine in glands and blood vessels indicated that peroxynitrite does not have a significant role in the vascular and glandular dysfunction of nasal polyps.

Topics: Adult; Case-Control Studies; Eosinophils; Female; Humans; Hypersensitivity, Immediate; Immunohistochemistry; Male; Nasal Mucosa; Nasal Polyps; Peroxynitrous Acid; Retrospective Studies; Tyrosine

To investigate the possible role of eosinophil peroxidase (EPO) in 3-nitrotyrosine (3NT) formation.. Observational study employing immunocytochemistry to assess the presence of 3NT, inducible nitric oxide synthase (iNOS), eosinophils, mast cells, neutrophils, and lymphocytes in ethmoid sinus mucosal biopsies from normal controls and subjects with allergic and nonallergic chronic sinusitis and nasal polyposis.. 3NT was more evident in biopsies from sinusitis patients (2.67 +/- 0.14, n = 21) than in healthy mucosa (0.43 +/- 0.2, n = 7, P < 0.01), but scores in atopic and nonatopic subjects were similar. Colocalization studies confirmed that 3NT was largely confined to eosinophils. No relationship was found between 3NT and other immune cells. 3NT detection was not correlated with the amount of immunostaining for iNOS.. Chronic sinusitis is accompanied by 3NT formation, which is largely restricted to the eosinophils, and likely driven by the action of eosinophil peroxidase, rather than by nitric oxide levels.. B-2.

Topics: Adult; Aged; Chronic Disease; Eosinophil Peroxidase; Eosinophils; Female; Humans; Male; Middle Aged; Nasal Polyps; Sinusitis; Tyrosine