Expression of cell proliferation and apoptosis gene associated protein on nasal polyps and its significance]

OBJECTIVE: To further understand the pathogenic mechanism of nasal polyps, namely the cells proliferation and apoptosis in nasal polyps tissue. METHODS: The proliferation cell nuclear antigen (PCNA), apoptosis associated gene protein (Bcl-2, Bax) were determined in 26 tissue samples of nasal polyps and 14 controls from normal inferior turbinates respectively. RESULTS: (1) The positive expression e of PCNA, Bcl-2 and Bax were significantly higher in epithelium of nasal polyps than the controls, and the expression rate of Bcl-2/Bax, however, tended equipoise. (2) The expression of Bcl-2 were significantly stronger than Bax in glands, eosinophils of nasal polyps tissue, and there were not significant differences in inferior turbinates. CONCLUSION: There is strongly proliferation activity in the epithelium of nasal polyps, and expression imbalance of Bcl-2/Bax may be one of the important factors of eosinophilia in nasal polyps tissue.     

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。     

Expression and distribution of Aquaporin 1 in the nasal polyps]

OBJECTIVE: To confirm the expression and distribution of Aquaporin 1 (AQP1) in the nasal polyps and to investigate the relation between AQP1 and the nasal polyp edema. METHODS: fourteen cases of normal inferior turbinates and 26 cases of nasal polyps were used. The expression and distribution of AQP1 in nasal polyps were examined by immunohistochemical technique. RESULTS: The level of AQP1 in the epithelial cells and serous cells from nasal polyps was higher than that in inferior turbinates, and the level of AQP1 in the epithelial cells and cilium cells from inferior turbinate was higher than that in nasal polyps. CONCLUSION: There is close relationship between AQP1 and nasal polyp edema.     

Fas及Bcl-2在鼻息肉组织中的表达及意义

目的：探讨Fas和Bcl 2在鼻息肉组织中的表达及与鼻息肉发病的关系。方法：应用S P免疫组化法检测36例鼻息肉组织及19例下鼻甲组织中Fas和Bcl 2的表达情况。结果： （1）Fas在鼻息肉上皮及腺上皮的表达弱于对照组（P＜0.05）；（2）Bcl 2在鼻息肉上皮及腺上皮的表达强于对照组（P＜0.05）；（3）鼻息肉上皮细胞中Fas、Bcl 2蛋白的表达无相关性（P＞0.05）。结论：（1）Fas和 Bcl 2在鼻息肉发生发展中起重要作用；（2）在NP上皮细胞中， Fas和Bcl 2无相关性，因此这两种凋亡基因在NP的形成过程中各起独立作用，协调抑制NP上皮细胞的凋亡。     

MUC5AC在人类鼻息肉及下鼻甲黏膜上皮的表达

目的 :探讨MUC5AC与鼻息肉及慢性肥厚性鼻炎黏液过量分泌的关系。方法 :免疫组织化学ABC法检测 2 7例鼻息肉、19例慢性肥厚性鼻炎下鼻甲及 9例正常下鼻甲黏膜上皮MUC5AC的表达。结果 :鼻息肉黏膜上皮及慢性肥厚性鼻炎下鼻甲黏膜上皮MUC5AC阳性细胞表达率明显高于正常下鼻甲黏膜上皮 (P <0 .0 5 ) ,且MUC5AC阳性表达细胞主要为杯状细胞。结论 :MUC5AC在鼻息肉及慢性肥厚性鼻炎下鼻甲黏膜上皮呈高表达 ,且阳性细胞为杯状细胞 ,表明MUC5AC确实对鼻息肉及慢性肥厚性鼻炎的黏液过量分泌起了一定作用。     

水通道蛋白1在鼻息肉组织中的表达

目的明确水通道蛋白1(Aquaporin1,AQP1)在鼻息肉组织的表达及分布并探讨其与鼻息肉组织水肿的关系.方法取正常下鼻甲组织14例和鼻息肉组织26例,4%多聚甲醛固定,石蜡包埋,连续切片,应用免疫组织化学技术检测AQP1蛋白在鼻息肉组织的表达及分布.结果鼻息肉组AQP1在血管内皮,浆液性腺中的阳性细胞表达率显著高于正常下鼻甲(P＜0.01);而下鼻甲组AQP1在上皮细胞层和纤毛细胞层的阳性细胞表达率显著高于鼻息肉组.结论提示AQP1在鼻息肉中的高表达与鼻息肉组织水肿的发生密切相关,具体调控机制有待进一步明确.     

HLA-DR and ICAM-1 expression and modulation in epithelial cells from nasal polyps

OBJECTIVE/HYPOTHESIS: Through human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1) expression, nasal epithelial cells could actively participate in the chronic inflammation and eosinophil infiltration observed in nasal polyps. The objective of the study was to evaluate HLA-DR and ICAM-1 expression in polyp epithelium and in a culture model of polyp epithelial cells allowing ciliated and secretory differentiation. STUDY DESIGN: Prospective non-randomized controlled in vitro study. METHODS: The in vitro HLA-DR and ICAM-1 expression was studied under basal conditions or after exposure to interferon-gamma, transforming growth factor-beta1, lipopolysaccharide, dexamethasone, or cetirizine. HLA-DR and ICAM-1 expression was investigated in situ by immunohistochemical staining of polyps and in vitro by immunofluorescent staining of cell cultures. HLA-DR and ICAM-1 were localized in cultured cells by confocal microscopy. Cultured cells expressing HLA-DR and ICAM-1 were quantified by flow cytometry. RESULTS: Both HLA-DR and ICAM-1 showed significant immunostaining of nasal polyp epithelium. In nasal polyp epithelial cell cultures, less than 5% of cells were positive for HLA-DR whereas 40% were positive for ICAM-1 at day 3. In vitro, HLA-DR was mainly located in the cytoplasm and ICAM-1 predominated on the apicolateral cytoplasmic membrane. Comparison of in situ and in vitro results showed that well-differentiated and poorly differentiated cells predominantly expressed HLA-DR and ICAM-1, respectively. Interferon-gamma significantly increased HLA-DR and ICAM-1 expression, whereas transforming growth factor-beta1 significantly decreased HLA-DR expression and lipopolysaccharide significantly increased ICAM-1 expression. CONCLUSION: HLA-DR and ICAM-1 epithelial expression in nasal polyps in situ and in vitro and their in vitro modulation reinforce the active role of epithelial cells in chronic inflammatory diseases of the upper airways.     

红霉素干预对人鼻息肉上皮细胞凋亡的影响

目的观察红霉素对体外培养的鼻息肉上皮细胞B细胞淋巴瘤-2基因(B cell lymphomas-2,Bcl-2)和Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)表达的影响,探讨上皮细胞凋亡在鼻息肉组织形成中的意义。方法将30例鼻息肉及15例下鼻甲组织均分成两组,分别对其上皮细胞进行原代培养,其中一组加入红霉素。培养第1、3、5天应用末端脱氧核苷酰转移酶介导的脱氧尿苷三磷酸原位缺口末端标记法(the TdT-mediated dUTP nick end labeling,TUNEL)检测细胞凋亡情况,并用免疫组化法检测细胞凋亡基因Bax、抑凋亡基因Bcl-2的表达。结果①鼻息肉红霉素组培养第1、3、5天的上皮细胞凋亡指数(用x±s表示,下同)分别为(33．23±6．50)％、(36．14±3．21)％和(52．63±7．86)％,对照组(不加红霉素组)为(31．02±5．60)％、(33．88±4．02)％和(39．64±7．48)％,培养第5天的上皮细胞凋亡指数红霉素组与对照组差异有统计学意义(t=4．480, P<0．05)。②鼻息肉上皮细胞Bcl-2和Bax表达均显著强于下鼻甲组织(P<0．01);培养第5天鼻息肉上皮细胞红霉素组Bax表达显著强于对照组(t=8．734,P<0．05),Bcl-2表达虽强于对照组,但差异无统计学意义;下鼻甲上皮细胞红霉素组与对照组的Bcl-2与Bax阳性表达差异均无统计学意义(P均>0．05);红霉素干预第5天鼻息肉上皮细胞显示明显的凋亡趋势(P<0．05)。结论红霉素能显著提高Bax蛋白的表达,有显著的促鼻息肉上皮细胞凋亡的作用。     

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     

Expression and distribution of aquaporin-2 in nasal polyps]

OBJECTIVE: To study the distribution and expression of aquaporion-2 (water channel protein; AQP-2) in nasal polyps and to evaluate the role of AQP-2 in the formation of nasal polyps. METHODS: Eleven samples of normal inferior turbinates and forty-six samples of nasal polyps were used. In the group of nasal polyps, there were ten cases of type II phase 1, twelve type II phase 2, ten type II phase 3 and fourteen type III. The expression of AQP-2 in both groups was studied with immunohistochemical technique. RESULTS: 1. Both the number of AQP-2 positive cells and the area density in the epithelial cell layer from nasal polyps were higher than those from inferior turbinates (P < 0.01, P < 0.05 respectively); In the group of nasal polyps, the area density from type III, type II phase 2 and type II phase 3 was significantly higher than that from type II phase 1 (P < 0.05); 2. Both the number of AQP-2 positive cells and the area density in the subepithelial tissue from type III, type II phase 2 and type II phase 3 nasal polyps were higher than those from type II phase 1 nasal polyps and inferior turbinates(P < 0.05), whereas the difference between the latter two was not significant(P > 0.05). CONCLUSION: The high expression of AQP-2 protein in nasal polyps may contribute to the genesis and development of nasal polyps.     

水通道蛋白-1在鼻息肉中的表达及其调节机制

目的：研究水通道蛋白-1(aquaporin1, AQP1)在鼻息肉组织中的表达,探讨其 与鼻息肉水肿形成及发展的关系。方法：取鼻中隔偏曲矫正术患者下鼻甲黏膜30例和鼻息肉组织60例。鼻息肉组Ⅱ型1期10例, 2期15例, 3期25例,Ⅲ型10例。采用免疫组织化学检测AQP1在不同类型及不同临床分期鼻息肉和下鼻甲黏膜组织中的表达及在不同类型鼻息肉组织中的表达。结果：（1）鼻息肉上皮层AQP1阳性细胞数显著高于下鼻甲黏膜(Ｐ＜0 01); 不同分型分期鼻息肉上皮层AQP1的阳性细胞数又有差异,Ⅱ型3期和Ⅲ型鼻息肉显著低于Ⅱ型1期鼻息肉(Ｐ＜0 01); 而在鼻息肉血管内皮及腺体细胞中的AQP1的表达明显高于下鼻甲(Ｐ＜0 01); （2）Ⅱ型3期和Ⅲ型鼻息肉血管内皮中AQP1阳性细胞数显著高于Ⅱ型1期鼻息肉和下鼻甲黏膜上皮下组织(Ｐ＜0 01)。结论：AQP1在鼻息肉组织中的异常表达可能与鼻息肉的发生和发展密切相关, 具体机制有待进一步研究。     

鼻息肉上皮细胞增殖活性和凋亡活性的比较

目的 探讨鼻息肉上皮细胞增殖和凋亡平衡状态及其发病学意义。方法 实验组（鼻息肉组）29例,对照组（下鼻甲组）11例,采用免疫组化染色法检测增殖细胞核抗原（proliferation cell nuclear antigen, PCNA）的表达。采用TUNEL过氧化酶原位标记法检测原位细胞凋亡。结果 ①鼻息肉上皮PCNA 阳性细胞指数（PIPCNA）和凋亡细胞指数（AI）均大于下鼻甲（30.02±5.89,5.33±2.79）(两者P＜0.01),但鼻息肉上皮PIPCNA/AI值（1.95±0.66）小于下鼻甲（6.93±3.32）(P＜0.01)。②鼻息肉上皮PIPCNA（53.60±11.10） 大于AI（29.48±8.20）(P＜0.01)。结论 鼻息肉上皮细胞增殖活性和凋亡活性均增强,凋亡活性增强幅度较大,但总的来说,鼻息肉上皮细胞增殖率仍然大于细胞凋亡率,细胞累积增多,导致了鼻息肉上皮细胞的过度增殖。     

Expression patterns of galectin-1 and galectin-3 in nasal polyps and middle and inferior turbinates in relation to growth regulation and immunosuppression

BACKGROUND: The term nasal polyposis describes benign growth processes in the nasal and sinus mucosa, which are mainly located in the middle meatus and never in the inferior meatus. As a step to define the biochemical determinants relevant for growth regulation, we focused on endogenous lectins known for anti-apoptotic (galectin-3) and immunomodulatory (galectin-1) activities. DESIGN: Using computer-assisted microscopy, we performed an immunohistochemical investigation defining the quantitative parameters of expression of galectin-1 and galectin-3 in 10 nasal polyps, 10 middle turbinates, and 10 inferior turbinates, all of which were obtained from surgical resection. RESULTS: Our data show that galectin-3 expression is markedly (P<.001) higher in nasal polyps than in turbinates. No relation to the allergic status was discovered. Galectin-1 expression is higher in nasal polyps than in middle turbinates (P<.001) in nonallergic patients compared with allergic ones (in glandular epithelium, P =.009; in connective tissue, P =.006). The lowest galectin-1 expression was observed in the middle turbinate. CONCLUSIONS: These data are in line with a positive influence of galectin-3 on growth and an immunoregulatory role of galectin-1, mimicking an increased expression dependent on glucocorticoid.     

Inflammatory cells in nasal mucosa and nasal polyps

OBJECTIVE: Since some controversy exists concerning the frequency of inflammatory cells in nasal polyps, we have compared the frequency of tissue inflammatory cells (lymphocytes, neutrophils, eosinophils and plasma cells) including 11 kinds of lymphocyte subsets in the same specimens of nasal mucosa and nasal polyps. METHODS: Histopathological observations and flow cytometric analyses were performed on eight mucosal specimens of the inferior turbinates of patients with nasal polyps and on 13 polyp specimens. RESULTS: Nasal polyps contained significantly more eosinophils, neutrophils and plasma cells than nasal mucosa, and EG2+ cells (activated eosinophils) were significantly more frequent in nasal polyps than in nasal mucosa. Flow cytometric analysis showed that there were no significant differences in the frequencies of lymphocytes and lymphocyte subsets (CD1+, CD2+, CD3+, CD5+, CD7+, CD4+, CD8+, CD10+, CD19+, CD20+ and HLA-DR+ cells) including CD4/8 ratios between nasal mucosa and polyps, though, both nasal mucosa and polyps contained significantly more lymphocytes than eosinophils, neutrophils or plasma cells. The T cell lineage (CD2+, CD3+, CD5+ and CD7+ cells) was found in high frequency and B cell lineage (CD10+, CD19+ and CD20+ cells) in low frequency in both nasal mucosa and polyps. The frequency of HLA-DR+ cells (most of which were activated T cells) was not significantly different between nasal mucosa and nasal polyps. CONCLUSION: Histopathological and flow cytometric analyses were performed on the composition of inflammatory cells in nasal mucosa of the inferior turbinates and in polyps from the same patients. The elevated numbers of activated eosinophils, neutrophils and plasma cells in nasal polyps compared with nasal mucosa suggest that inflammatory processes play important roles in the pathophysiology of nasal polyps. The frequencies of lymphocytes and lymphocyte subsets were not significantly different between these two tissues.     

两种细胞外基质糖蛋白在鼻息肉中的表达

OBJECTIVE: To explore the role of tenascin (TN) and fibronectin (FN) in the pathophysiology of nasal polyp. METHODS: The expression of TN and FN in nasal polyps from 34 patients and in inferior turbinates from 20 patients with deviation of nasal septum was studied with immunohistochemical method. In patients with nasal polyps, the relations between expression and histopathologic characteristics, eosinophilias (EOS) infiltration, clinical staging and the size of nasal polyps were analyzed. RESULTS: (1) The gray score of TN and FN expression was 163.10 +/- 10.54 and 163.24 +/- 11.52 in nasal polyps respectively, whereas it was 175.49 +/- 9.29 and 173.93 +/- 7.92 in inferior turbinates respectively. The difference between two groups was significant(P < 0.01); (2) The expression of TN and FN in edematous type was significantly stronger than that in cystic fibrous and glandular type (P < 0.05); (3) The association between FN expression and EOS infiltration was significant(r = -0.60, P < 0.01); (4) The expression of TN and FN did not correlate with clinical staging and size(P > 0.05). CONCLUSION: Abnormal ECM may contribute to proliferation of epithelium, accumulation of EOS and edema formation, as a result, to enhance the development of nasal polyps.     

血管通透性因子在鼻息肉中的表达及意义

目的 探讨血管通透性因子（ｖａｓｃｕｌａｒ ｐｅｒｍｅａｂｉｌｉｔｙ ｆａｃｔｏｒ，ＶＰＦ）在鼻息肉组织中的表达及意义。方法 将９例鼻息肉标本及８例下鼻甲粘膜标本行ＶＰＦ及其受体ｆｌｋ－１的免疫组化染色，光镜观查。结果 ＶＰＦ在鼻息肉组织的血管内皮细胞和腺体细胞的表达明显高于下鼻甲组织（Ｐ〈０．０１，Ｐ〈０．０５），ｆｌｋ－１在血管内皮细胞的表达明显高于下鼻甲组织（Ｐ〈０．０１）。结论 ＶＰＦ对鼻