鼻息肉中总IgE及IL-5与嗜酸性粒细胞浸润的相关性研究

目的探讨鼻息肉中总IgE、IL-5的表达、嗜酸性粒细胞(eosinophils,EOS)浸润情况及其相关关系,以分析其在鼻息肉发病中的作用.方法采用免疫组化SP法检测38例鼻息肉,15例正常鼻腔黏膜组织中总IgE阳性细胞分布情况;酶联免疫吸附试验(ELISA)检测鼻息肉中IL-5含量;Chromotrope 2R特染法检测鼻息肉中EOS浸润情况.结果①鼻息肉组织中总IgE、IL-5及EOS水平均明显高于正常鼻腔黏膜组织,P均＜0.01;②鼻息肉组织中总IgE与EOS、IL-5与EOS以及IL-5与总IgE之间均呈明显正相关关系,相关系数r分别为0.843,0.642,0.667,P均＜0.01.结论EOS浸润在鼻息肉的形成和发展中起重要作用,而IgE及IL-5则对鼻息肉中EOS浸润发挥重要影响.     

鼻息肉中IgE及GM-CSF与嗜酸粒细胞浸润的相关性研究

目的:探讨鼻息肉组织中IgE和粒细胞巨噬细胞集落刺激因子(GM-CSF)的表达对嗜酸粒细胞浸润聚集的作用及二者的关系及意义。方法:采用免疫组织化学SP法检测30例鼻息肉标本(鼻息肉组)和11例下鼻甲部分切除术患者下鼻甲黏膜标本(对照组)组织中IgE阳性细胞分布情况;酶联免疫吸附法检测上述标本中GM-CSF含量,同时观测2组组织中嗜酸粒细胞的浸润程度。结果:鼻息肉组中IgE、GM-CSF水平及嗜酸粒细胞数均明显高于对照组(均P<0.01),且IgE与GM-CSF的水平分别与鼻息肉组织中嗜酸粒细胞浸润数呈正相关(r=0.65、0.62,均P<0.01),鼻息肉组中IgE与GM-CSF水平呈正相关(r=0.52,P<0.01)。结论:鼻息肉是以嗜酸粒细胞浸润为特征的疾病过程,IgE及GM-CSF则对鼻息肉中嗜酸粒细胞浸润发挥重要作用,IgE介导的Ⅰ型变态反应在鼻息肉的形成和发展中占有重要地位。     

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。     

鼻息肉中总IgE与嗜酸粒细胞浸润的相关性研究

目的:探讨总IgE及嗜酸粒细胞(EOS)在鼻息肉中的表达及其相关关系,以分析其在鼻息肉发病中的作用。方法:采用免疫组织化学SP法检测38例鼻息肉、15例中鼻甲黏膜组织中总IgE阳性细胞表达;采用Chromotrope2R染色法检测EOS浸润情况。结果:①鼻息肉组织中总IgE及EOS水平均明显高于中鼻甲黏膜组织,均P<0.01;②鼻息肉组织中总IgE与EOS呈明显正相关关系(r=0.843,P<0.01)。结论:EOS浸润在鼻息肉的形成和发展中起重要作用,IgE介导的Ⅰ型变态反应对鼻息肉中EOS浸润发挥一定作用。     

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。     

TNFα及VCAM-1在鼻息肉中的表达及其与嗜酸性粒细胞浸润的关系

目的 :研究鼻息肉组织中肿瘤坏死因子α(TNFα)和血管活性细胞粘附分子 - 1(VCAM- 1)的表达及其相关性 ,探讨二者与鼻息肉嗜酸性粒细胞浸润的关系。方法 :分别以 TNFα和 VCAM- 1的单克隆抗体对 2 2例鼻息肉组织 (鼻息肉组 )和 16例慢性鼻炎鼻粘膜组织 (对照组 )进行免疫组织化学染色。结果 :TNFα和 VCAM- 1在鼻息肉组中的表达明显高于对照组 (P <0 .0 5 ) ,且二者呈正相关 (P <0 .0 1)。鼻息肉组中 VCAM- 1的表达与嗜酸性粒细胞浸润程度一致 (P <0 .0 1)。结论 :TNFα通过上调血管内皮细胞 VCAM- 1的表达 ,从而促进嗜酸性粒细胞与内皮细胞的粘附 ,穿内皮迁移 ,进而加剧鼻息肉组织中嗜酸性粒细胞的浸润。     

蛋白激酶C在鼻息肉组织嗜酸性粒细胞浸润增多中的调控作用

目的 :探讨蛋白激酶C(PKC)何种亚型对鼻息肉组织中嗜酸性粒细胞 (EOS)浸润增多具有调控作用。方法 :采用原位杂交法和免疫组织化学MGG染色 ,观察 2 6例鼻息肉组织中PKC几种亚型PKCα、PKCβ1、PKCβ2 、PKCγ的表达 ,分析何种亚型在鼻息肉EOS增多中起调控作用。 结果 :2 6例鼻息肉组织EOS中均有PKC表达 ,且与Bcl 2mRNA及其蛋白成正相关 (r1=0 .0 87 5 ,r2 =0 .0 82 3,P <0 .0 1) ,其中PKCα为强表达 ,而PKCβ1、PKCβ2 为弱表达 ,PKCγ则不表达。结论 :EOS增多主要是由于激活了PKC这一信号传导途径 ,使EOS凋亡受到抑制、生存延长 ,致使其数量增多 ,且主要是PKC亚型中的PKCα在鼻息肉组织EOS增多中起调控作用     

鼻腔应用布地奈德对鼻息肉中IL-5表达的作用

目的 :观察鼻腔应用布地奈德治疗对鼻息肉中 IL - 5表达的影响 ,深入了解糖皮质激素类药物局部治疗对鼻息肉的作用机制。方法 :采用免疫组化 ABC法 ,观察经布地奈德治疗 6～ 8周和未经治疗的鼻息肉组织 (各 16例 )中 ,IL -5阳性细胞的浸润和分布状况。结果 :鼻息肉组织固有层中可见 IL - 5阳性细胞表达 ,且多为嗜酸性粒细胞 ,IL - 5阳性细胞密度与嗜酸性粒细胞的浸润程度密切相关 (y=14.782 + 2 .0 0 2 x,r=0 .6 48,P <0 .0 1)。经布地奈德治疗的鼻息肉组织中 IL - 5阳性细胞的浸润程度有下降的趋势 ,但与未治组织的差异未达显著性水平 (P >0 .0 5 )。结论 :1IL - 5的表达与嗜酸性粒细胞的浸润密切相关 ,嗜酸性粒细胞是鼻息肉组织中 IL- 5的来源之一 ;2鼻腔应用布地奈德 6～ 8周治疗可能抑制鼻息肉中 IL- 5表达。     

粒细胞巨噬细胞集落刺激因子和白细胞介素5在鼻息肉中表达

目的探讨粒细胞巨噬细胞集落刺激因子(granuIocyte-macrophage colony-stimulating factor,GM-CSF)和白细胞介素5(interleukin-5,IL-5)在单发鼻息肉组织及多发鼻息肉组织中的表达水平的差异。方法分别采用ELISA法及免疫组化SP法检测单发鼻息肉组30例、多发复发鼻息肉组23例及对照组15例(下鼻甲部分切除术患者下鼻甲黏膜标本)中GM- CSF及IL-5的表达状况。结果多发性鼻息肉组中GM- CSF及IL-5表达量均明显高于单发鼻息肉组,单发鼻息肉组明显高于对照组,两组间差异均有统计学意义(P<0.01)。结论鼻息肉的多发、复发机制可能与GM- CSF及IL-5的高表达水平有关,它们在鼻息肉的发病机制中占有重要地位。     

嗜酸性粒细胞及IL5在上颌窦后鼻孔息肉与鼻息肉中表达的差异

目的 通过对比上颌窦后鼻孔息肉(ACP)、伴变应性鼻炎的鼻息肉(NPwAR)及不伴变应性鼻炎的鼻息肉(NPsAR)组织中嗜酸性粒细胞浸润及IL5的表达水平,探讨嗜酸性粒细胞及IL5在不同鼻腔炎性疾病发生中作用的差异。 方法 对10例ACP、9例NPwAR及14例NPsAR组织切片行H&E染色,对嗜酸性粒细胞的浸润进行计数;提取组织总RNA,通过实时荧光定量核酸扩增检测系统(QPCR)对组织中IL5的mRNA表达水平进行检测。 结果 嗜酸性粒细胞在ACP中的浸润显著低于NPwAR(P<0.001),嗜酸性粒细胞在ACP中浸润百分比的中位数低于NPsAR,但两者间差异无统计学意义;嗜酸性粒细胞在NPwAR中的表达水平显著高于NPsAR(P<0.05)。在ACP组织中IL5的mRNA表达水平显著低于NPsAR(P<0.05)和NPwAR(P=0.001),且NPsAR组织中IL5的mRNA表达水平显著低于NPwAR(P<0.05)。 结论 ACP与NP的发病机制有所不同。嗜酸性粒细胞及IL5参与了NP的发病过程,并与变应性鼻炎的发生密切相关,但在ACP的形成中可能未起到重要作用。     

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.     

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.     

Nasal polyposis: from cytokines to growth

Nasal polyposis (NP) is a chronic inflammatory condition that is mostly characterized by an infiltration of eosinophils. How this eosinophilic inflammation leads to polyp formation remains largely unclear. In order to identify the most important factors in polyp growth, first we report the histologic features of two early stage manifestations of eosinophilic nasal polyps compared to their surrounding normal mucosa and mature polyps from the same patients. Histomorphologic analysis of these early stage manifestations of NP showed the presence of eosinophils, forming a subepithelial cap over a pseudocyst area that was filled with albumin. In mature NP, a large pseudocyst area containing albumin was surrounded by subepithelial eosinophilia. Second, in an approach to quantify and to study possible relations between eosinophilic inflammation and changes in extracellular tissue components we measured interleukin-5 (IL-5), eotaxin, eosinophil cationic protein (ECP), leukotrienes (LTC4/D4/E4), transforming growth factor-beta 1 (TGF-beta 1), fibronectin, hyaluronic acid, and albumin in nasal tissue homogenates of 31 subjects. Nasal polyp samples (n = 16) were obtained during routine endonasal sinus surgery, whereas control non-polyp samples (n = 15) from subjects with (6) and without (9) allergic rhinitis were obtained from the inferior turbinate during septum surgery. In the group of polyp patients 11 received no treatment, whereas 5 were treated with oral glucocorticoids (GCS) within 4 weeks before surgery. IL-5 was measurable in 8 of 11 untreated NP, whereas IL-5 could not be detected in all 15 controls nor in 4 of 5 oral corticoid-treated polyps. The comparison between the untreated polyp group and controls showed significantly higher concentrations of IL-5, eotaxin, ECP, and albumin in polyp supernatants, whereas TGF-beta 1 was significantly lower. In the oral GCS-treated group, ECP and albumin were significantly reduced compared to untreated nasal polyps. The same tendency, but not reaching significance, was seen for eotaxin and fibronectin, while no difference was found for LTC4/D4/E4 and hyaluronic acid between the groups. Our observations suggest a deposition of albumin (and possibly other plasma proteins) and extracellular matrix proteins, which may be regulated by the subepithelial eosinophilic inflammation, as a possible pathogenic principle of polyp formation and growth. IL-5 and eotaxin are found to be key factors for eosinophilic accumulation and activation in NP. Oral corticoid treatment may lead to the shrinkage of NP by downregulation of the eosinophilic inflammation and reduction of the extravasation and deposition of albumin in NP.     

鼻息肉组织中白细胞介素—5和粒细胞巨噬细胞集落刺激因子水平测定及其意义

OBJECTIVE: To study the relationship between the concentration of interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulation factor (GM-CSF) in nasal polyps and its significance. METHODS: The concentration of IL-5, GM-CSF was measured by enzyme linked immunosorbent assay (ELISA) in a total of 38 cases, and the number of eosinophils were counted in the same tissues. RESULTS: The statistical analysis showed that the concentrations of IL-5 and GM-CSF have significant difference (P < 0.05) between the nasal polyps and the control group. There is a positive correlation between the quality of IL-5/GM-CSF and the extent of eosinophils (r = 0.75/0.71). CONCLUSION: This study demonstrated that there are inductive compartments, namely the microenvironment, in which immune-effector and inflammatory cell function is modulated in nasal polyps. A special discussion has been made of eosinophils and IL-5/GM-CSF in the formation of nasal polyps, and the effect of the IL-5/GM-CSF in the accumulation of eosinophils.     

Immunological features of patients with polypous ethmoiditis

34 patients with nasal polyps (NP) and 12 normal individuals were studied immunologically to investigate association of nasal polyp formation with disorders of general and local immunity. In NP patients there were decreased preoperative and early postoperative levels of peripheral blood T- and B-lymphocytes, functional activity of lymphocytes and neutrophils. In contrast to normal individuals, nasal secretion of NP patients contained degenerative epithelial cells and neutrophils, activated lymphocytes, monocytes and eosinophils. Nasal polyp tissues obtained after polypectomy contained more B-lymphocytes than T-lymphocytes. Lymphocytes and neutrophils in nasal polyps had elevated functional activity in tissue culture. We conclude that local hyperactivation of T- and B-lymphocytes as well as neutrophils contribute much to nasal polyp formation.     

Eotaxin synthesis by nasal polyp fibroblasts

Nasal polyps is a chronic inflammatory disease of the upper airway characterized by structural abnormalities including stromal fibrosis. Fibroblasts are a rich source of cytokines and inflammatory mediators and are thought to play an important role in the development of fibrosis. In addition, there is considerable evidence for the participation of eosinophils in the pathophysiology of nasal polyps. Although increased numbers of eosinophils are present in nasal polyps, the mechanisms responsible for their selective accumulation are not completely clear. Eotaxin is a chemokine that promotes the selective recruitment of eosinophils. Thus, it may be an important molecule for the recruitment of eosinophils in nasal polyps. The purpose of this study was to investigate whether nasal polyp fibroblasts synthesize eotaxin after stimulation with lipopolysaccharide, IL-1beta or TNF-alpha. Using primary nasal polyp tissue-derived fibroblast lines, we demonstrated that LPS, IL-1beta and TNF-alpha induced the gene expression and protein production of eotaxin in nasal polyp fibroblasts. This responsiveness to LPS, IL-1beta and TNF-alpha was time- and dose-dependent. These findings support the hypothesis that fibroblasts could play an important role in the recruitment of eosinophils in nasal polyps through the production of eotaxin.