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.     

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。     

STAT6在鼻息肉组织中的表达及其与嗜酸粒细胞浸润的关系

目的：研究信号转导和转录激活因子6（STAT6）在鼻息肉组织中的表达及其对嗜酸粒细胞（EOS）浸润聚集的作用,探讨其在鼻息肉发生中的可能作用。方法：选取符合纳入标准的鼻息肉患者手术切除标本（鼻息肉组）30例和同期单纯行鼻中隔偏曲矫正术中切除的下鼻甲组织（对照组）10例。采用免疫组织化学SP法检测2组下鼻甲黏膜中STAT6的表达。应用SPSS13.0软件进行统计学分析。结果：STAT6和EOS在鼻息肉组织中的表达明显高于下鼻甲,差异有统计学意义（P〈0.05）。STAT6阳性细胞主要集中于鼻息肉的上皮细胞、腺体细胞和组织中浸润的炎性细胞的细胞质中。鼻息肉组中STAT6的表达与EOS浸润程度一致（P〈0.01）。结论：STAT6在鼻息肉组织中的高表达及其对EOS浸润聚集的作用,可能与鼻息肉的发生和发展关系密切。     

白细胞介素-5与嗜酸性粒细胞阳离子蛋白在鼻息肉发病中的意义及相互关系

目的：探讨白细胞介素—5(IL—5)及嗜酸性粒细胞阳离子蛋白(ECP)在鼻息肉发病中的作用及相互关系。方法：采用pharmacia CAP荧光免疫系统和ELISA双抗体夹心法对30例鼻息肉患者(鼻息肉组)和8例鼻中隔偏曲或阻塞性睡眠呼吸暂停综合征(OSAS)患者(对照组)分别进行血清中ECP及组织匀浆中ECP、IL—5的检测。结果：鼻息肉组匀浆中IL—5的水平明显高于对照组，其差异有显著性意义(P＜0．05)；鼻息肉组血清与匀浆中的ECP含量明显高于对照组，其差异亦有显著性意义(P＜0．05)。鼻息肉组匀浆中IL—5与血清中ECP水平呈明显正相关(r＝0．598，P＜0．05)；与匀浆中的ECP水平也呈正相关(r＝0．451，P＜0．05)。结论：ECP是嗜酸性粒细胞活化的标志，也是导致鼻腔炎症发生的重要因子；IL—5在鼻息肉组织中高表达，并与血清和组织中ECP水平密切相关，共同促进鼻腔炎症过程的不断加重。     

转化生长因子β1和基质金属蛋白酶及其组织抑制物在慢性鼻窦炎和鼻息肉组织中的差异性表达

目的:探讨转化生长因子β1(TGF-β1),基质金属蛋白酶1、7、9(MMP-1、7、9)及其组织抑制物-1(TIMP-1)在慢性鼻窦炎和鼻息肉以及正常下鼻甲黏膜组织中表达程度的差异。方法:采用酶联免疫吸附试验(ELISA)检测22例慢性鼻窦炎筛窦黏膜、21例鼻息肉和15例下鼻甲黏膜组织中TGF-β1,MMP-1、7、9以及TIMP-1的蛋白表达量,并比较他们在不同组织中表达程度的差异。结果:①TGF-β1、MMP-7、MMP-9及TIMP-1在慢性鼻窦炎和鼻息肉组织中的表达均比正常下鼻甲黏膜组织增高,差异具有统计学意义(均P<0.05);②慢性鼻窦炎组织中TGF-β1和TIMP-1相比鼻息肉组织中的表达增高,差异具有统计学意义(P<0.01和P<0.05);③鼻息肉组织中MMP-7的表达比慢性鼻窦炎组织中的表达增高,差异具有统计学意义(P<0.01)。结论:慢性鼻窦炎和鼻息肉组织显示出不同的TGF-β1、MMP-7、TIMP-1蛋白表达水平。     

鼻息肉中CD34的表达及其与嗜酸粒细胞浸润的关系

目的 探讨CD34在人鼻息肉组织中的表达及其与嗜酸粒细胞浸润的关系。方法 采用HE和免疫组化ElivisionPlus二步法，检测30例正常下鼻甲，60例鼻息肉组织中CD34蛋白的表达情况，并对CD34阻性血管进行微血管（MVD））计数，了解微血管的分布及嗜酸粒细胞的浸润情况。结果 鼻息肉组织中CD34阳性表达广泛，正常下鼻甲组织中CD34呈散在的弱阳性表达；鼻息肉组织中MVD明显高于下鼻甲组织中MVD（P〈0．01），与嗜酸粒细胞的浸润具有正相关性。结论 CD34蛋白有可能介导嗜酸粒细胞的浸润，加重对鼻黏膜的损害。     

催乳素在鼻息肉巨噬细胞中的表达及意义

OBJECTIVE: To detect the expression level and distribution of prolactin (PRL) in nasal polyp and to find out the significance of the mechanism of PRL in the invasion of nasal polyp. METHODS: Twenty-five polyp tissues were obtained from the patients who were subjected to nasal polypectomy in our Department. Inferior turbinate mucosa was used as control obtained from 12 patients with rhinogenous snoring. HE staining was performed for routine histopathologic examination. The expression of PRL in nasal polyps was observed by immunohistochemical staining, and six polyp tissues were estimated through double staining for determining cells which expressed PRL. RESULTS: (1) Positive expression of PRL was significantly stronger (t =4.004, P < 0.01) in 25 nasal polyp tissues (2.05 +/- 0.88) than that in 12 normal inferior turbinate mucosa (0.96 +/- 0.50). Positive expression of macrophage (CD68) was significantly stronger (t = 3.519, P < 0.01) in 25 nasal polyp tissues (1.85 +/- 0.83) than that in 12 normal inferior turbinate mucosa (0.93 +/- 0.52). (2) The PRL expressing cell mainly was the macrophage as demonstrated by double immunohistochemical method. CONCLUSION: PRL derived from macrophages of nasal mucosa may participate in the formation of nasal polyp through its local immune modulation.     

鼻息肉组织嗜酸粒细胞中水通道蛋白-1和抗凋亡基因Bcl-2 mRNA的表达及意义

OBJECTIVE: To study the significance of aquaporin-1 (AQP-1) expression in the eosinophils of nasal polyps. The expression and location of AQP-1 mRNA and apoptosis associated gene Bcl-2 mRNA in nasal polyps were explored. METHODS: Sixteen nasal polyp samples were collected from 11 women and 5 men aged 20-65 years during routine endonasal surgery. Nasal mucosa specimens from the inferior turbinates of 10 patients with allergic rhinitis (7 women and 3 men, aged 16-58 years), collected during septoplasty, were used as controls. The expression of AQP-1 mRNA and Bcl-2 mRNA was detected in serial adjacent sections by in situ hybridization and eosinophils were examined by stain MGG. RESULTS: AQP-1 mRNA expression was found in all 16 nasal polyps and in 4 of 10 inferior turbinate tissues, the mean expression rates were (93.16 +/- 13.25)% and (19.54 +/- 4.98)%, respectively. All 16 nasal polyps and 10 control nasal tissues expressed Bcl-2 mRNA, by the average rates of (84.74 +/- 12.10)% and (16.45 +/- 3.12)%, respectively. The expression of AQP-1 mRNA was positively correlated with Bcl-2 mRNA expression in nasal polyps (r = 0.875, P < 0.01). CONCLUSIONS: AQP-1 contributes to the survival of eosinophils in nasal polyps by keeping the permeation balance of eosinophils.     

The pathogenesis of nasal polyposis by immunoglobulin E and interleukin-5 is completed by transforming growth factor-beta1

OBJECTIVES/HYPOTHESIS: Nasal polyps are benign mucosal protrusions into the nasal cavity of multifactorial origin and are characterized by chronic mucosal inflammation. The suggested multifactorial pathological mechanisms comprise several factors including cytokines and immunoglobulin E (IgE). The study was designed to examine the suggested roles of IgE, interleukin-5 (IL-5), and transforming growth factor-beta1 (TGF-beta1) in the pathogenesis of nasal polyposis. METHODS: Nasal polyps (n = 34) and healthy nasal mucosa samples (n = 9) were taken during routine endonasal surgeries. Immunoglobulin E (n = 13), IL-5 (n = 22), and TGF-beta1 (n = 27) concentrations were measured with enzyme-linked immunosorbent assay technique in homogenized polyp tissue and in control mucosa. Atopic and nonatopic groups were selected and compared. Histomorphological examination and immunohistochemical analysis to detect IL-5 and TGF-beta1 were performed in five specimens. RESULTS: The level of tissue-bound IgE was significantly higher in polyps compared with control specimens and in atopic compared with nonatopic polyps, but between nonatopic polyps and control specimens the difference was not significant. However, significant correlation was found between tissue and serum IgE in the complete polyp (P =.001) and atopic polyps group (P =.05). Tissue IL-5 concentration was significantly higher in polyps compared with control specimens, in which it was below the limit (15 pg/mL), and there was no difference between atopic and nonatopic polyps. In atopic polyps there was significant correlation between tissue IgE and IL-5. Transforming growth factor-beta1 concentration proved to be significantly higher in control mucosa than in polyps, with no difference between atopic and nonatopic polyps. Immunohistochemical analysis revealed numerous IL-5-positive eosinophil cells and TGF-beta1 positivity in the lamina propria of polyp samples, but none in control specimens. CONCLUSIONS: High tissue TGF-beta1 quantity in healthy nasal mucosa without its active form on the cell surface and its low quantity in polyps may reflect its essential role in the inhibitory mechanisms of nasal polyposis. Interleukin-5 plays a key role in the eosinophil recruitment and activation, and both atopic and nonatopic pathways might activate this process. The main sources of IL-5 and TGF-beta1 are the eosinophils and macrophages. Immediate hypersensitivity, besides other mechanisms, might be related to atopic polyps, but the involvement of other, local allergic mechanisms in IgE production of nonatopic polyp tissue cannot be excluded.     

鼻息肉调节激活正常T细胞表达和分泌因子的测定及其意义

目的 探讨在鼻息肉形成过程中,上皮应答时产生调节激活正常Ｔ细胞表达和分泌因子（ｒｅｇｕｌａｔｅｄ ｕｐｏｎ ａｃｔｉｖａｔｉｏｎ,ｎｏｒｍａｌＴｃｅｌｌ ｅｘｐｒｅｓｓｅｄ ａｎｄ ｓｅｃｒｅｔｅｄ,ＲＡＮＴＥＳ）对嗜酸粒细胞趋化、移行、局部聚集的影响。方法 采用无血清原代细胞培养法培养鼾症患者下鼻甲上皮细胞和鼻息肉上皮细胞,经炎性介质ＩＬ－１β（２５ｕｇ／Ｌ,５０ｕｇ／Ｌ）刺激后收集２４ｈ和４８     

The up-regulated expression of tenascin C in human nasal polyp tissues is related to eosinophil-derived transforming growth factor beta1

BACKGROUND: Tissue remodeling is an important characteristic of nasal polyps (NPs). However, the mechanisms underlying the remodeling processes are poorly defined. This study investigated the role of transforming growth factor (TGF) beta1 and eosinophils in the expression of tenascin C (Tn-C), an extracellular matrix glycoprotein, in NPs. METHODS: The protein expression of Tn-C and TGF-beta1 was examined by means of immunohistochemistry in NPs and normal control inferior turbinate tissues. Furthermore, cell culture, quantitative RT-PCR, and in situ immunocytofluorescence techniques were used to investigate the direct effect of TGF-beta1 and eosinophils on Tn-C production in primary nasal epithelial cells. RESULTS: Tn-C protein expression was significantly up-regulated in NP tissues and correlated with TGF-beta1+ eosinophils. TGF-beta1 and eosinophils dramatically induced Tn-C mRNA and protein expression in nasal epithelial cells. The effect of eosinophils could be inhibited partly by a neutralizing antibody to TGF-beta1. CONCLUSION: Eosinophil-derived TGF-beta1 may contribute, at least in part, to the tissue remodeling in NPs.     

鼻黏膜中Toll样受体5的表达

目的研究鼻黏膜中Toll样受体5(Toll-likereceptor-5,TLR-5)的表达以了解TLR-5在鼻黏膜天然免疫中的作用。方法鼻息肉和下鼻甲组织从接受鼻内镜手术治疗的慢性鼻及鼻窦炎和鼻中隔偏曲患者取得。应用免疫组化法检测17例鼻息肉和13例下鼻甲黏膜中TLR-5蛋白的表达,应用实时荧光定量RT-PCR(real-time fluorescentquantitative RT-PCR,real-time FQ-RT-PCR)检测14例鼻息肉和9例下鼻甲黏膜中TLR-5 mRNA的表达。结果在所有标本中均检测到TLR-5 mRNA和蛋白表达。免疫组化显示TLR-5蛋白主要表达于鼻黏膜上皮细胞和腺体上皮细胞。在细胞核和细胞浆中均有表达。在鼻黏膜上皮,染色最强的区域位于黏膜上皮表面一侧的细胞膜和细胞核。另外在间质单核样炎症细胞及NK细胞也有表达。鼻息肉组织中TLR-5蛋白表达指数5.529±0.653较下鼻甲2.346±0.619增高,差异有统计学意义(Z=-3.107,P=0.002)。结论本次研究确认了TLR-5在鼻黏膜和鼻息肉组织的表达,鼻息肉组织中TLR-5表达的增高可能与鼻息肉内持续的炎症状态有关。提示TLR-5有可能成为鼻息肉、慢性鼻及鼻窦炎一个新的治疗靶点。     

Expression of ecalectin, a novel eosinophil chemoattractant, in nasal polyps

CONCLUSION: Ecalectin, which is produced in the mucosa of nasal polyps, seems to play an important role in the accumulation and activation of eosinophils in nasal polyps, regardless of the presence or absence of atopic predisposition. OBJECTIVE: Ecalectin is a recently discovered eosinophil chemoattractant which elongs to the galectin family. We investigated the expression of ecalectin in nasal polyp tissues associated with various nasal and paranasal diseases in order to clarify the pathogenesis of eosinophilia in nasal polyposis. MATERIAL AND METHODS: Nasal polyps were taken from 56 patients diagnosed as having chronic sinusitis with nasal polyposis. The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin. RESULTS: The number of EG2- and ecalectin-positive cells was significantly higher in nasal polyps than control turbinates. Ecalectin-positive cells were observed in the subepithelial layer, where many EG2-positive cells were present. The number of ecalectin-positive cells correlated significantly with the number of EG2-positive cells in nasal polyps. Many ecalectin mRNA-positive cells were also observed in nasal polyps with an accumulation of EG2-positive cells.