Histamine,norepinephrine and serotonin content of nasal polyps

Histamine, norepinephrine and serotonin were assayed and localized by fluorescence histochemistry in normal mucosa and nasal polyps because of their possible role in the development of inflammation and edema. Histamine was present in greater concentration in nasal polyps than in normal mucosa. Norepinephrine was present primarily in the base of nasal polyps and in greater concentration than in normal mucosa. Patients with aspirin sensitivity and asthma had much lower histamine concentrations in their nasal polyps than all other patients with nasal polyps. A proposal for a possible mechanism of formation of nasal polyps based on vascular and inflammatory mechanisms and incorporative roles for histamine and norepinephrine is presented.     

Cholinergic muscarinic receptor in the nasal mucosa of guinea pigs with bronchial asthma with and without hypersensitive nasal symptoms

Using [3H]-quinuclidinyl benzilate (QNB) as a radioligand, receptor binding assay was performed to evaluate the changes of the muscarinic receptor in the nasal mucosa of guinea pigs sensitized with toluene diisocyanate (TDI), which showed hypersensitive airway symptoms both in the lower airway and in the nose. The same study was performed in guinea pigs sensitized with bacterial crystalline alpha-amylase (BCA) which showed typical symptoms of bronchial asthma but without hypersensitive nasal symptoms. In the nasal mucosa of guinea pigs sensitized with TDI, an increased density of the muscarinic receptor was confirmed with no change in affinity of the receptor. However, in the nasal mucosa of guinea pigs sensitized with BCA, no changes were observed either in the density of the muscarinic receptor of the nasal mucosa or in its affinity. The increased density of the muscarinic receptor observed in subjects with nasal allergy, which was reported earlier, is not specifically related to IgE-mediated nasal allergy and is not induced by systemic sensitization itself but is assumed to be induced by some pathophysiological changes in the nasal mucosa including antigen-antibody reaction with development of hypersensitive nasal symptoms.     

Expression of the voltage-dependent chloride channel ClC-3 in human nasal tissue

In the present study, ClC-3, one of the voltage-dependent chloride channels, was identified in human nasal tissue. In situ hybridization and immunohistochemical investigations demonstrated the localization of ClC-3 in the serous acini and ductal portions of submucosal nasal glands, which are the primary source of nasal secretion. Our data suggest that this channel contributes to nasal secretion via chloride transport. Its dysfunction might lead to abnormal nasal secretion in such pathological states as sinusitis.     

Histamine threshold and nasal hyperreactivity in non specific allergic rhinopathy

The authors studied the histamine threshold (endpoint concentration for a 100% pressure gradient increase at a flow of 0.25 liter/second) in a group of 29 patients suffering from non specific allergic rhinopathy and a control group of 15 normal subjects. The result of the nasal challenge was measured with two different methods of rhinomanometry: the passive anterior rhinomanometry (P.A.R.) and the active anterior rhinomanometry (A.A.R.). There existed a slightly significant difference (P less than or equal to 0.05) in histamine threshold between the patient and the control group. The 21 in duplo performed histamine challenges showed the very good reproducebility of the method. Finally, the A.A.R. method turned out to be slightly more sensitive than the P.A.R.-method.     

Arachidonic acid metabolism in nasal tissue and peripheral blood cells in aspirin intolerant asthmatics.

Aspirin intolerance (AI) is characterized by polypous rhinosinusitis, bronchial asthma and adverse reactions to aspirin. The common intolerance to all cyclo-oxygenase inhibitors allows us to focus study of the pathogenesis of AI on the metabolism of arachidonic acid (AA). We studied the metabolism of AA in nine aspirin intolerant asthmatics (AIA) and eight healthy volunteers (controls) by measuring prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT = LTC4/D4/E4) in nasal tissue and peripheral blood cells (PBCs) using a specific immunoassay. In all patients with AI the tests were performed before and after bronchial provocation with lysine-ASA. In the control group the tests were done before and after 500 mg ASA p.o. The release of pLT in nasal polyps of AIA was found to be significantly higher than in normal mucosa of AIAs and controls. In every tissue a significant increase of pLT after aspirin challenge was observed. Nasal polyps of AIA show a significantly lower release of PGE2 than normal mucosa of AIAs and controls. Peripheral blood cells of AIA show a significantly higher release of pLT and a significantly lower release of PGE2 than PBCs of controls. Therefore clinical manifestations of AI may be based on an alteration of AA metabolism in AIA.     

The concentration and expression of IL-5 in human nasal polyp tissue]

OBJECTIVE: To study the concentration and expression of IL-5 in nasal polyp tissues and explore its significance in the micro-environment differentiation of eosinophils accumulation and clarify the conception of nasal polyposis. METHODS: The concentration and expression of IL-5 in nasal polyp tissues of 40 patients were determined by ELISA and immunohistochemistry, and inferior turbinate mucosa from patients with nasal polyps and healthy volunteers was used as control. RESULTS: 1. IL-5 concentration in the polyp tissues was significantly higher than that in inferion turbinate mucosa(P < 0.05). There was no significant difference in inferion turbinate mucosa between the patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 concentration in polyp tissues was markedly higher in patients with extensive polypoid change of nasal mucosa, history of previous polypectomy and allergic rhinitis compared with those without these features (P < 0.05). IL-5 concentration had no correlation with age and sex (P > 0.05). 2. 80.1% of the eosinophils were positive for IL-5 and 90.9% of IL-5 positive cells were eosinophils. Only 3.7% of the lymphocytes and neutrophils were IL-5 positive, and IL-5 was not detectable in epithelial cells. IL-5 expression in eosinophils of polyp tissues was remarkably stronger than that of the turbinate mucosa (P < 0.05). There was no significant difference in inferion turbinate mucosa between the patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 expression of eosinophils in polyp tissues was significantly stronger in patients with extensive polypoid change of nasal mucosa, history of previous polypectomy and allergic rhinitis compared with those without these features (P < 0.05). There was no significant difference in IL-5 expression in lymphocytes and neutrophils between polyp tissues and inferior turbinate nasal mucosa (both P > 0.05). CONCLUSION: IL-5 is a key protein in eosinophilic pathologic mechanisms in nasal polyp tissues.     

鼻息肉组织中转化生长因子β亚型的表达及意义

目的探讨转化生长因子β(transforming growth factor,TGF-β)亚型在鼻息肉病患者的息肉组织中的表达和分布，以了解其在上呼吸道慢性炎症过程中的作用。方法采用免疫组化碱性磷酸酶和抗碱性磷酸酶(alkaline phospatase andanti-alkaline     

人下鼻甲微血管内皮细胞的体外培养及鉴定

目的:研究人下鼻甲微血管内皮细胞的体外培养方法,为鼻腔、鼻窦相关疾病的研究提供实验基础。方法:采用手术中获得的人下鼻甲边缘黏膜及黏膜下组织,机械分离和酶解消化微血管内皮细胞,在体外条件下进行培养。分别行细胞形态学观察、细胞生长曲线的测定和培养细胞免疫荧光鉴定。结果:体外培养条件下得到人下鼻甲微血管内皮细胞,经细胞形态学观察、细胞生长曲线测定及免疫荧光鉴定证实为血管内皮细胞。结论:本研究获得的体外培养人下鼻甲微血管内皮细胞,可为鼻腔过敏性疾病和炎症性疾病的微血管病理改变及药物对鼻腔下鼻甲微血管功能影响等研究提供实验基础。     

Histamine H1 receptor and reactivity of the nasal mucosa in sensitized guinea pigs.

OBJECTIVE: Nasal Hypersensitivity to histamine is higher in allergic patients than that in normal control, suggesting that affinity and/or density of H1 receptors in nasal mucosa may be increased in patients with allergic rhinitis. The purpose in this study is to examine the correlation between the hyperresponsiveness and number of histamine H1 receptors in guinea pig nasal mucosa. METHODS: Guinea pigs were sensitized by DNP-Ascaris antigen. To block histamine H1 receptors, ketotifen was used and the number of receptors was counted by receptor binding assay technique. These data were compared with nasal airway volume (VOL) assessed by acoustic rhinometry of the same animals to know whether the number of H1 receptors is correlated to the nasal responsiveness to the antigen, or not. Eighty animals were divided into five groups which are composed of nonsensitized and sensitized group pretreated with saline, 0.1, 1.0 and 10 mg/kg of ketotifen, respectively. RESULTS: The number of H1 receptors (Bmax) was significantly increased in sensitized group compared with that in control. It decreased dose dependently by pretreatment of ketotifen. The percent change of VOL showed - 31.1 +/- 4.1% at 10 min and - 42.9 +/- 4.1% at 30 min after antigen challenge in sensitized animals. This was dose dependently inhibited by ketotifen. There was a highly inverse correlation between VOL and Bmax (r = -0.708, P< 0.0001). CONCLUSION: These results suggest that sensitization increases the number of histamine H1 receptor, and that increased number of H1 receptor in nasal mucosa in sensitized guinea pigs may be one of the causes of nasal hyperresponsiveness to antigen.     

Significance and expression of transforming growth factor beta in human nasal polyp tissue]

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of transforming growth factor beta (TGF-beta) in human inflammatory nasal polyps. METHODS: TGF-beta 1-3 in nasal polyp tissues and inferior turbinate mucosa of twenty-five polyposis patients were detected with immunohistochemistry alkaline phosphatase and anti-alkaline phosphatase (APAAP) method. The inferior turbinate mucosa of eight healthy volunteers were selected as control. Six polyp tissues were estimated with double immunolabeling and Western-blot analysis to compare the characterization of the TGF-beta isoforms expression and the proportion of macrophages and eosinophils in nasal polyp tissues. RESULTS: The expression of TGF-beta 1-3 in nasal polyps was significantly higher than that in nasal mucosa and indetecable in nasal mucosa from healthy volunteers; TGF-beta 1 was the main isoform detected in nasal polyps; TGF-beta positively was accompanied by numerous macrophage and eosinophil infiltration. CONCLUSIONS: TGF-beta mainly TGF-beta 1 is strongly expressed in nasal polyps and its mucosa, where it could be produced by macrophages and eosinophils. TGF-beta could induce modification of epithelium and connective tissue and therefore be involved in the pathogenesis of nasal polyposis.     

Ectopic tonsillar tissue in the nasal septum

A rare case of hypertrophied lymphoid tissue in the nasal septum considered to be an ectopic tonsil was reported. The patient was a 53-year-old male, and a polypoid mass attached to the septal wall by a stalk was removed. Histological examination showed that the tumour was an ectopic hyperplastic tonsil presenting in the nasal septum. The pathogenesis of this tumour was not clear, but it was considered as hyperplasia or a new formation of primary or secondary lymphoid follicles. This is the first case report of such a rare condition.     

Tenascin在鼻息肉组织中的表达及其临床意义

目的：探讨Tenascin(TN)在鼻息肉组织中的表达和分布特征及其在鼻息肉发生中的可能作用。方法：采用免疫组化链霉菌抗生物素蛋白—过氧化物酶(SP)法检测24例鼻息肉标本(鼻息肉组)和15例慢性肥厚性鼻炎下鼻甲标本(下鼻甲组)中TN的表达，并以5例健康者(对照组)下鼻甲黏膜作对照。结果：鼻息肉组和下鼻甲组黏膜上皮细胞及腺上皮细胞均表达TN；鼻息肉组TN的黏膜上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；鼻息肉组TN的腺上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；对照组下鼻甲组织中黏膜上皮及腺体几乎检测不到TN的表达；鼻息肉组腺体TN阳性率明显高于下鼻甲组(P＜0．05)。结论：TN在鼻息肉组织中的高表达与鼻息肉的发生、发展相关；TN在鼻腔内的表达细胞是黏膜上皮细胞和浆液性腺上皮细胞。     

Monoclonal antibody-detectable carbohydrate epitopes of human nasal secretions are differentially expressed in tissue and diseases

To study the differential carbohydrate expression of airway secretions, we have produced a series of monoclonal antibodies that recognize human nasal secretory cell products. Mice were immunized with purified nasal secretion from patients with chronic sinusitis (CS) and hybridomas were selected by ELISA and immunohistochemical staining of the maxillary sinus mucosa from patients with CS. Eighteen antibodies were obtained. Antibody HCS 18 reacted with epithelial goblet cells, antibody HCS 4, 5, 6, and 16 stained submucosal gland cells, and antibody HCS 13 and 15 reacted with epithelial goblet cells, submucosal gland cells, and endothelial cells of vessels. The other eleven antibodies recognized epithelial goblet cells and submucosal gland cells. Cross-reactivity of these antibodies with secretory cells in other organs and in other species was determined and the different staining pattern was observed between upper and lower airway tissue, suggesting that secretory products from upper and lower airways may be different. Reactivity of the antibodies with nasal secretory cells was also examined in patients with perennial allergic rhinitis (AR) and normal subjects. Antibody HCS 18 weakly reacted with nasal glands in the tissue from CS and AR patients, but minimally reacted with gland cells in normal tissue. Antibody HCS 1 and 7 partially lost their reactivity with nasal epithelium of inferior turbinate from normal subjects and AR patients. These antibodies may be useful to study nasal secretions.     

Cytotoxic effects of nasal buserelin on nasal mucosal tissue in rabbits

To investigate the cytotoxic effects of nasal buserelin on rabbit nasal mucosal tissue, twenty-four female rabbits were studied prospectively. The rabbits were divided into 4 groups including 6 rabbits. The rabbits’ left noses were included in the all study groups: 150?μg/puff/day of buserelin acetate was administered topically twice daily during 21, 42 and 63?days. Saline was administered topically twice daily to the left nasal cavity in the control group. The nasal septal mucosal stripe tissue was carefully removed from underlaying cartilage after sedation. HE staining, Masson’s trichrome, toluidine blue and TUNEL staining were used to evaluate mucosal changes. Each preparation was investigated via apoptotic cells, and they were accounted. Kruskal–Wallis test was used to evaluate nonparametric comparison of apoptotic cells. Mononuclear cells have been raised in the sub-epithelial connective tissue, nucleuses of epithelial cells in the apical region were pyknotic, and apoptotic cells were determined on 21-day group. In the 42-day group, nasal epithelial tissue was similar to 21-day group and epithelial cells including pyknotic nucleus were present in this group, too. In the 63-day group, epithelial cells were light colored. Venous sinuses in the sub-epithelial connective tissue were wide but not congested and not raised collagen filaments. In the intra-epithelial tissue, some of cells were TUNEL (+). Apoptotic cells were fewer in the control group according to 21-day group. In 42- and 63-day groups, these cells were fewer than in 21-day group. Numerical difference was present between the groups, but statistical significance was not found between the groups. We concluded that nasal buserelin cytotoxicity was not potent in the nasal cavity in rabbits. We use nasal buserelin in all indications with confidence.     

Histamine induces nasal obstruction via calcitonin gene-related peptide in sensitized guinea pigs

The purpose of this study was to characterize the late phase nasal obstruction that is induced by a nasal histamine challenge in sensitized guinea pigs. The volume of the nasal cavity was measured using an acoustic rhinometer. A nasal histamine challenge to unsensitized animals induced nasal obstruction at 30 minutes after the challenge while a challenge to sensitized animals induced nasal obstruction not only at 30 minutes but also at 4-6 hours. Histamine (measured by high-performance liquid chromatography), cysteinyl leukotriene (enzyme-linked immunosorbent assay (ELISA)), prostaglandin D2 (ELISA), eosinophils and basophilic cells of sensitized guinea pigs were not changed in the late phase after histamine challenge. Administration of pyrilamine, a histamine H1 receptor antagonist, and calcitonin gene-related peptide (CGRP) (8-37), a CGRP-1 receptor antagonist, significantly improved histamine-induced nasal obstruction at 30 minutes and in the late phase, respectively. These results suggest that a nasal histamine challenge induces nasal obstruction not only immediately through the histamine H1 receptors but also in a late phase via CGRP.     

Histamine and the nasal vasculature: the influence of H1 and H2-histamine receptor antagonism

The aim was to determine the effect of H₁-and H₂-receptor blockade on histamine-induced changes in nasal airways resistance and levage protein concentrations. Normal subjects were pretreated with oral cetirizine or ranitidine in a double-blind and randomized manner. Measurements of the concentration of total protein and albumin in nasal a lavage fluid together with nasal airway resistance were made before and after challenge. any effect of treatment was assessed by comparing the areas under the time-response curves. In all nine subjects available for analysis histamine caused an immediate increase in all measurements. Ranitidine reduced the maximum increase in nasal airway resistance, but this effect was significant only in combination with cetirizine. The increase in lavage total protein and albumin concentrations was almos completly abolished by cetirizine, whereas ranitidine had less effect. We conclude that the histamine H₁-receptor has the greatest effect on changes in nasal vascular permeability induced by topical histamine, whereas the H₂-receptor has the greatest effect on nasal obstruction.