Roles of CD43, CD20 and local IgE in the pathogenesis of nasal polyps]

OBJECTIVE: To estimate the roles of CD43, CD20 and total IgE in the pathogenesis of nasal polyps. METHOD: Twenty-six cases of nasal polyps and 20 cases of mucosa of middle turbinates were used in present study. RESULTS: The number of CD43+ cells, CD20+ cells and plasma cells in nasal polyps were significantly more than that in middle turbinates (P < 0.01). The positive rate of local IgE+ cells in nasal polyps was significantly higher than in middle turbinate (P < 0.01). CONCLUSION: There were active cellular immunity and humoral immunity in nasal polyps. Local allergy may play a role in the pathogenesis of nasal polyps.     

鼻息肉组织中T—细胞亚群的分布及2种白细胞介素表达？…

目的 探讨Ｔ－淋巴细胞及细胞因子白细胞介素（ｉｎｔｅｒｌｅｕｋｉｎ,ＩＬ）调节２功能的紊乱在鼻息肉发病中的重要作用。方法 应用免疫组织化学的方法检测３２例鼻息肉标本和６例下鼻甲粘膜对照标本中Ｔ－细胞亚群（ＣＤ＾＋４和ＣＤ＾＋８细胞）以及细胞因子ＩＬ－５、ＩＬ－１０阳性细胞的表达情况。并进行统计学分析。结果 鼻息肉组织中可见各种炎细胞浸润,ＣＤ＾＋４和ＣＤ＾＋８细胞数增多（Ｐ〈０．００１）;其中ＣＤ     

Isolation and phenotypic characterization of mucosal nasal lymphocytes by direct ex vivo analysis

Cellular inflammation of the nasal mucosa demonstrates a local immune response which plays an important role in allergic rhinitis. The aim of the present study was to characterize nasal mucosal lymphocytes regarding their activation and differentiation state by direct ex vivo flowcytometric analysis. Lymphocytes from the inferior turbinates were isolated by a mechanical method of preparation and, for comparison, from peripheral blood by Ficoll gradient centrifugation. Patients suffering from rhinitis or difficulty in nasal breathing were divided into an allergic (pollen-allergy, n = 13) and non-allergic group (n = 24). Expression of different T- and B-cell markers was determined by flowcytometric analysis. CD4+ T-cells from the nasal mucosa exhibited a memory phenotype (CD45RO+, 97%), were highly activated (CD69+, 43–73%), and showed low expression of the cutaneous lymphocyte antigen (CLA+, 5%). Nasal CD20+ B-lymphocytes expressed significantly higher levels of mIgE and lower levels of CD23 and CD80 than peripheral B-cells. Subsets of CD80+ (4%) and CD86+ (6%) CD20+ B-lymphocytes were identified in the nasal mucosa. No significant differences between allergic and non-allergic individuals were determined. As expected, the data show profound phenotypical differences between circulating peripheral blood and nasal mucosal lymphocytes. Activated memory lymphocytes are present in the nasal mucosa from allergic, but also non-allergic patients and may indicate to a significant role of a local inflammatory state without systemic criteria for allergy. In our study, we show that direct ex vivo isolation of lymphocytes is practicable method and offers a new technique to examine the local nasal allergic immune response using a multiparametric phenotypical analysis. Christin Wolfram and Claudia Rasche contributed equally to this work.     

复发性鼻息肉中T淋巴细胞亚群的表达

目的 :检测复发性鼻息肉组织中T淋巴细胞亚群的表达 ,探讨T淋巴细胞介导的免疫反应在鼻息肉复发中所起的作用。方法 :应用荧光免疫流式细胞术检测 17例复发性鼻息肉患者鼻息肉组织、外周血T淋巴细胞亚群CD4 、CD8 、CD4 5RO 的表达 ,并与正常人下鼻甲黏膜及外周血的相应指标进行比较。 结果 :复发性鼻息肉组织中有大量T淋巴细胞浸润 [(39.6 5±2 .0 8) % ],而在健康下鼻甲黏膜中几乎未见CD3 细胞。在复发性鼻息肉中 ,CD3 CD4 细胞[(6 4.4 46± 5 .2 97) % ]多于CD3 CD8 细胞 [(35 .5 5 4± 5 .2 97) % ](P <0 .0 5 ) ,CD3 CD4 5RO 细胞 [(2 2 .6 49± 2 .789) % ]也显著多于正常人外周血CD3 CD4 5RO 细胞 [(3.896± 0 .384 ) % ](P<0 .0 5 ) ,CD3 CD4 /CD3 CD8 比值为 1.95 6± 0 .0 93,复发性鼻息肉患者外周血比值为 2 .36 7±0 .12 8,正常人外周血比值为 1.6 0 6± 0 .0 96 ,其差异均有统计学意义 (均P <0 .0 5 )。结论 :复发性鼻息肉组织中有大量T淋巴细胞表达 ,且T细胞亚群比例失调 ,显示细胞免疫功能的紊乱在鼻息肉的形成与复发中起重要作用     

CD43CD20及总IgE在鼻息肉组织中表达的研究

目的　探讨CD4 3 、CD2 0 及总IgE在鼻息肉组织中的表达 ,分析其在鼻息肉发病中的作用。方法　采用免疫组化SP法及HE染色对 2 5例鼻息肉和 2 0例中鼻甲粘膜进行研究。结果　鼻息肉组织中CD 43 细胞和CD 2 0 细胞、浆细胞数显著多于中鼻甲粘膜组织 (P <0 0 1) ,总IgE阳性表达率为44 %,显著高于中鼻甲粘膜组织的 10 %(P <0 0 5 )。结论　鼻息肉中存在活跃的细胞免疫和体液免疫 ,鼻粘膜局部变态反应可能参与鼻息肉的发病。     

Expression of CD68 CD45RO CD20 and proliferating cell nuclear antigen in nasal polyps]

OBJECTIVE: To study the cellular expression of CD45RO, CD20, CD68 and proliferating cell nuclear antigen (PCNA) in nasal polyps. METHODS: Nasal polyp tissues from 50 patients were evaluated for cellular expression of CD45RO, CD20, CD68 and PCNA using immunohistochemistry SP by counting the average number in 5 chosen high-power fields, Histopathological observations were combined with HE. Analyses were performed on SPSS10.0. RESULTS: CD68+ cells were expressed more in nasal polyps dominated by eosinophils than by neutrophils(P < 0.05). There was no difference between CD45RO and CD20, but both of them had negative correlation(P = 0.05). Significant correlation was found between CD68+ cells and eosinophils or PCNA positive cells on epithelium. PCNA positive cells on epithelium had significant correlation on fibroblast (P < 0.05). CONCLUSION: Inflammatory cell infiltration (eosinophilia CD45RO, CD20, CD68) and cell proliferating in epithelium cells, glandular cell and fibroblast are strongly correlated with formation of nasal polyps. The nasal polyps are not only characteristic of eosinophilia but also by lymphocytes dominated by CD45RO and CD68 positive cells. CD68 may be stem cell of nasal polyp.     

巨噬细胞和淋巴细胞及增殖细胞核抗原在鼻息肉组织中的表达及病理学意义

目的　研究巨噬细胞 (CD68)、T细胞 (CD45RO)、B细胞 (CD2 0 )和增殖核细胞核抗原(proliferatingcellnuclearantigen ,PCNA)在鼻息肉组织中的表达。方法　应用免疫组化链霉菌抗生物素蛋白过氧化酶 (strept avidinoxidase,SP)法对 50例鼻息肉分别做CD2 0、CD45RO、CD68、PCNA的免疫组化染色 ,结合常规HE染色切片进行分析。结果　①CD68+ 细胞在嗜酸性粒细胞性鼻息肉较嗜中性粒细胞性鼻息肉表达率高 ,差异具有显著性意义 (P <0 0 5) ;②CD45RO、CD2 0在鼻息肉均有阳性表达 ,CD45RO与CD2 0呈负相关 (P =0 0 5) ;③CD68阳性细胞与嗜酸性粒细胞浸润及鼻息肉上皮PCNA阳性表达有相关性 (P <0 0 5)。鼻息肉上皮的PCNA阳性表达和成纤维细胞PCNA阳性表达有相关性 ,(P <0 0 5)。结论　鼻息肉的形成与炎性细胞浸润密切相关。鼻黏膜局部的细胞免疫与体液免疫异常导致上皮细胞、成纤维细胞增殖、腺体增生是鼻息肉发生的基础 ,CD68+ 细胞可能是鼻息肉中的炎性干细胞     

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.     

鼻息肉组织中炎性细胞的病理学意义

研究鼻息肉组织中炎性细胞的病理意义。方法对１０例正常鼻粘膜和２４例鼻息肉组织行免疫组化及ＭＧＧ染色以观察嗜酸性粒细胞,单核细胞,巨噬细胞在组织中的分布程度,结果：鼻息肉组织中嗜酸性粒细胞,ＣＤ６８阳性巨噬细胞和单核细胞显著增加。结论：鼻息肉的发生与炎性细胞的浸润,活化密切相关,药物治疗应是鼻息肉病治疗中的一个重要方面。     

CD34在鼻息肉组织中的表达及意义

目的 检测CD34在鼻息肉组织中的表达,探讨CD34+细胞在鼻息肉上皮修复和炎症反应中的作用.方法 采用免疫组织化学方法检测10例鼻息肉组织和10例对照中鼻甲黏膜组织中的表达.结果 4例鼻息肉上皮基底细胞可见CD34表达,在中鼻甲黏膜上皮中未见CD34表达.在鼻息肉和对照中鼻甲黏膜上皮下固有层中可见到CD34+炎症细胞...     

鼻息肉的组织病理学特征及其发病机制

目的观察鼻息肉的组织细胞学特征,探讨鼻息肉的发病机制。方法应用常规组织学方法及甲苯胺蓝特殊染色法观察134例鼻息肉组织中嗜酸性粒细胞、淋巴细胞、浆细胞、中性粒细胞和肥大细胞的浸润情况,并进行计数、分组及统计学处理。结果:134例鼻息肉组织中嗜酸性粒细胞聚集型有69例,占51.49%,淋巴细胞聚集型有52例,占38.81%,混合型有10例,占7.46％;中性粒细胞聚集型有3例,占2.24％。4组间嗜酸性粒细胞数、淋巴细胞数、肥大细胞数、中性粒细胞数和浆细胞数差异均有统计学意义(P＜0.01)。嗜酸性粒细胞数与肥大细胞数呈负相关(r＝－0.534,P＜0.01),淋巴细胞数与肥大细胞数呈正相关(r＝0.601,P＜0.01),浆细胞数与肥大细胞数呈正相关(r＝0.202,P＜0.05)。结论鼻息肉中嗜酸性粒细胞聚集似乎与肥大细胞及Ⅰ型变态反应无关, 各种炎性细胞的浸润及相互作用是导致鼻息肉发生发展的重要环节,鼻息肉的组织病理学分型对探讨鼻息肉的发病机制有一定帮助。     

Effect of proinflammatory cytokines on human leucocyte antigen expression of epithelial cells of nasal polyps]

OBJECTIVE: To explore the effect of proinflammatory cytokines on the expression of human leucocyte antigen(HLA-DR) in epithelial cell of nasal polyps. METHODS: The samples were from 23 patients with nasal polyps and 11 cases of normal inferior turbinates. The samples were fixed, paraffin-embeded and sectioned for observing distribution of HLA-DR positive cells. Nasal epithelial cells were obtained after enzymatic digestion and cell culture was performed for observing influences of interleukin (IL)-1 beta and tumor necrosis factor (TNF-alpha) to expression of HLA-DR of epithelial cells and the effect of dexamethasone(10(-5) mol/L). RESULTS: The HLA-DR expression in epithelium was significantly stronger in nasal polyps than that in inferior turbinates. The expression of HLA-DR in cultured cells under stimulation of proinflammatory cytokines was increased compared with controls, but the expression was more intense in nasal polyps than that in inferior turbinates. Increased HLA-DR expression under stimulation of cytokines was reduced significantly by dexamethasone. CONCLUSION: The epithelium is in a key position to participate in inflammatory and immunologic events in the airways. Epithelial cells potentially contribute to airway inflammation by antigen presentation and the production of proinflammatory cytokines.     

Clinical aspects and distribution of immunologically active cells in the nasal mucosa of patients with nasal polyps after endoscopic sinus surgery and treatment with topical corticosteroids

Summary Clinical parameters of 72 patients who were operated upon for nasal polyps were evaluated as well as biopsy specimens of the mucosa of the middle and inferior turbinates of 41 of these patients. Biopsies were taken at the time of endoscopic sinus surgery (ESS), after 6 months and after 1 year in 23 patients. During the follow-up period the patients were treated with topical corticosteroids (budesonide). At the time of ESS significantly more CD8+ (suppressor/cytotoxic) cells than CD4+ (helper/inducer) cells were found in the middle and inferior turbinates. At 6 months significantly more CD4+ cells were found than at the time of ESS, whereas at 1 year the number of CD4+ cells had decreased and was lower than at 6 months. These data support the theory that the occurrence of nasal polyps is associated with T-cell-dependent disturbances. Clinical evaluation revealed that most of the patients with chronic airway obstruction had better pulmonary functions postoperatively or required less medication for lung disease. These findings show that ESS combined with topical corticosteroids has a positive effect on upper and lower respiratory tract pathology. Correspondence to: A. E. Stoop     

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.     

Expression and localization of the inducible isoform of nitric oxide synthase in nasal polyps

Nitric oxide (NO) and peroxynitrite play an important role in pathophysiology of several airway diseases. An inducible isoform of nitric oxide synthase (iNOS) is known to be expressed in the nasal mucosa in allergic and chronic rhinitis. Few reports exist, however, on the expression of iNOS in nasal polyps. We detected and localized iNOS expression in nasal polyp tissue. Nasal polyps were obtained from 10 patients following polypectomy, and divided into allergic and infectious groups based on clinical presentation and laboratory testing. One nasal mucosa of the inferior turbinate was also obtained from a cadaver without nasal disease. iNOS expression was studied by immunohistochemistry under light and electron microscopy. Immunoreactivity for iNOS was localized to the mucosal epithelium, inflammatory cells, vascular endothelium and smooth muscle, and nasal gland. Strong immunoreactivity was shown in the mucosal epithelium of both groups, and weak to moderate reactivity in the mucosal epithelium of the inferior turbinate. Vascular endothelium and smooth muscle of both groups sometimes showed weak to moderate immunoreactivity. Nasal glands of both groups sometimes showed weak immunoreactivity. A significant difference between allergic and infectious groups was observed in predominant types of inflammatory cells. Neutrophils were predominant in the infectious group (p < 0.01), and eosinophils in the allergic group (p < 0.0001). About 50%-53% in allergic and 42% in infectious groups--of inflammatory cells showed positive immunoreactivity for iNOS. Immunoreactive cells were neutrophils, eosinophils, and macrophages. Lymphocytes, plasma cells, and mast cells invariably reacted negatively. A significant difference between allergic and infectious groups was observed in predominant iNOS-immunoreactive cells. Ratios of immunoreactive neutrophils to all neutrophils (p < 0.05) and to all inflammatory cells (p < 0.05) were significantly higher in the infectious group. The ratio of immunoreactive eosinophils to all inflammatory cells was significantly higher in the allergic group (p < 0.0001), while the ratio of immunoreactive eosinophils to all eosinophils did not differ between infectious and allergic groups. The ratios of immunoreactive macrophages to all macrophages and to all inflammatory cells did not differ significantly between groups. Electron microscopy showed that degenerated cells with pyknotic nuclei were located next to immunoreactive eosinophils, suggesting the cytotoxicity of NO, peroxynitrite, or superoxide.     

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。     

Activated T cells in the nasal mucosa of patients with grass-pollen allergy. A pilot study.

Six patients with grass-pollen allergy were provoked with water-soluble grass pollen until a pronounced allergic reaction occurred. This was performed outside the grass-pollen season, and the allergen was administered on the edge of the inferior turbinate. Biopsies were taken both before provocation and during the reaction, 15-30 minutes after provocation. The nasal population of immunohistochemically positive cells for HLA-DR, CD1, interleukin-2-receptor, IgE, CD4 and CD8 were studied. There was a marked increase of IL2-R-positive cells (activated T lymphocytes) in the nasal mucosa after provocation, whilst the other cell populations approximately remained unchanged (apart from a certain increase of IgE). The increase of activated T lymphocytes may imply that certain subsets of T cells play a role in the allergic response, and that the role of helper T cells very likely is much more complex than the regulation of mast cells and eosinophils. The concomitant presence of Langerhans' cells (CD1-positive) and activated T lymphocytes may indicate a possible association on site between an antigen-presenting cell and both effector as well as memory cells in allergic reactions.     

细胞间粘附分子在鼻息肉组织中的表达及意义

目的 探讨以嗜酸粒细胞浸润为病理特征的鼻息肉组织中局部细胞间粘附分子的表达及其意义。方法 对９例正常鼻粘膜和１９例鼻息肉组织冰冻切片，用细胞间粘附分子１和淋巴细胞功能相关抗原１单抗进行免疫组织化学及其与ＭＧＧ双染，光镜观察，结果 与对照组相比，鼻息肉组织ＩＣＡＭ－１和ＬＦＡ－１的表达均显著增加，组织局部ＩＣＡＭ－１的表达与大量ＬＦＡ－１阳性的嗜酸粒细胞浸润密切相关。结论 鼻息肉组织ＩＣＡＭ－１和Ｌ     

Expression, localization, and significance of vascular permeability/vascular endothelial growth factor in nasal polyps

BACKGROUND: The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. OBJECTIVE: To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. METHODS: Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. RESULTS: The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. CONCLUSION: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.     

影响鼻息肉手术疗效的相关因素探讨

目的：探讨鼻息肉的不同组织病理学表现与经内镜手术疗效的关系。方法：通过对鼻息肉常规病理分析，及CD20、CD45、RO、CD68、增殖细胞核抗原的免疫组化染色结果，结合临床资料及术后随访资料，应用SPSS10．0统计软件中的秩和检验、非参等级相关性检验，极大似然比后退法进行Logistic回归分析。结果：单因素分析只有CD68^ 、鼻息肉总积分对治愈率有显著影响。多因素分析CD68^-、鼻息肉总积分和淋巴细胞、嗜酸性粒细胞浸润程度与手术疗效有显著相关性。结论：伴有腺体增生的鼻息肉其总积分、嗜酸性粒细胞、淋巴细胞、CD68^-细胞浸润程度可作为鼻息肉患者预后是否容易复发的指标。