Vascular endothelial growth factor and children featuring nasal polyps

BACKGROUND: The aim of this study is to explore the expression of vascular endothelial growth factor within nasal polyps, and the implication of such expression as regards the development of nasal polyps amongst children. MATERIAL AND METHODS: Sixty children suffering from chronic rhinosinusitis were enrolled in this study. Amongst them, 30 patients featured rhinosinusitis with associated nasal polyps. A biopsy specimen was taken from the stalk or the base of the nasal polyp for nasal-polyp sufferers, and the ethmoid sinus for study participants who featured no nasal polyps. The primary lesions biopsied were immunohistochemically stained with a specific endothelial-cell marker and also stained for the presence of vascular endothelial growth factor. The specific level of vascular endothelial growth factor and the mean number of blood vessels present in a visual microscopic (biopsied-specimen) field were calculated under light microscopy (x400). RESULTS: The number of vascular endothelial growth factor-expressing cells for the nasal-polyp group and for the sinusitis group was, respectively, 20.8+/-4.0 and 11.5+/-3.4 per visual field. Correspondingly, the mean intra-polyp blood-vessel density for the nasal-polyp group and that for the control group was, respectively, 10.5+/-2.6 and 5.0+/-1.9 per visual field. The mean intra-polyp blood-vessel density and the number of vascular endothelial growth factor-expressing cells proved to be significantly greater amongst individuals from the nasal-polyp group than was the case for their analogs from the sinusitis group (P<0.01, for both). The presence of vascular endothelial growth factor was found to be distributed predominantly within the vascular endothelium and the mast cells of polyp tissue. In addition, the level of vascular endothelial growth-factor expression and the mean blood-vessel count per field correlated significantly for nasal-polyp tissue (P<0.001). Furthermore, the relative size of nasal polyps correlated significantly with the number of (intra-polyp) vascular endothelial-cell growth factor-expressing cells and the mean blood-vessel density (P<0.05, for both). CONCLUSION: The level of expression of vascular endothelial-cell growth factor (VEGF) and the mean blood-vessel density were shown to be significantly greater within nasal polyps than within corresponding sinusitis mucosa. Clinically, the expression of both of these parameters correlated well with the relative size of nasal polyps. Vascular endothelial growth factor participates in the formation of nasal polyps amongst children suffering from chronic rhinosinusitis (CRS).     

Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non-asthmatic patients

The cause of nasal polyps remains unknown, although there is a well-recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty-four asthmatic and 35 non-asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.     

鼻息肉中单核细胞趋化蛋白1和血管内皮生长因子的表达

目的明确单核细胞趋化蛋白1（monocyte chemotactic protein 1，MCP-1）和血管内皮生长因子（vascular endothelial growth factor，VEGF）在鼻息肉组织中的表达及其相关性，初步探讨MCP-1与鼻息肉发生的关系。方法取40例鼻息肉组织和25例下鼻甲组织，应用原位杂交和免疫组织化学等方法检测MCP-1和VEGF mRNA及蛋白质的表达。结果鼻息肉组织中MCP-1和VEGF mRNA及蛋白质的表达均高于对照组下鼻甲组织（P值均〈0．01）；鼻息肉组织中MCP-1和VEGF蛋白质的表达呈正相关（r=0．871，P〈0．05）。结论鼻息肉组织中MCP-1和VEGF表达增加，二者协同作用可能是鼻息肉形成的原因之一。     

黏附分子及血管内皮生长因子在鼻息肉中的表达

目的 探讨细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）以及血管内皮生长因子（VEGF）在鼻息肉中的表达与意义。方法25例鼻息肉标本和9例下鼻甲黏膜标本，分别行ICAM-1、VCAM-1、VEGF免疫组化染色和HE染色，光镜下观察比较各种分子表达水平。结果 鼻息肉中可见大量嗜酸性粒细胞（EOS）浸润。ICAM-1、VCAM-1和VEGF均可表达于鼻息肉血管内皮、间质及炎症细胞，且在鼻息肉血管内皮、间质及浸润炎症细胞中的表达趋势呈现正相关关系。结论 ICAM-1、VCAM-1可能与EOS等炎症细胞附壁浸润活化过程关系密切，VEGF可能启动并加强这一病理变化。它们的协同作用可能参与了鼻息肉的病理过程。     

Activated eosinophils in nasal polyps: a comparison of asthmatic and non‐asthmatic patients

Objectives: There is a recognized clinical association between nasal polyps and asthma. Nasal polyps and the airways of asthmatic patients demonstrate marked eosinophilia suggesting that this inflammatory cell may have a key role to play in both conditions. The objective of this study was to determine whether nasal polyps from patients with asthma had a greater density of activated eosinophils than patients with no associated respiratory disease. Design: Archived specimens were retrieved from patients who had undergone nasal polyp surgery and their case notes reviewed. Activated eosinophils were identified using immunohistochemistry for a monoclonal antibody to secreted eosinophil cationic protein (EG2). Setting: Teaching hospital otolaryngology unit. Participants: Consecutive patients who had undergone nasal polyp surgery in 1994 were recruited. The diagnosis of asthma was based on a documented physician diagnosis and appropriate drug treatment. Twenty‐four asthmatic and 35 non‐asthmatic patients were studied. Main outcome measures: Eosinophil density was measured using a standardized counting technique. Results: Asthmatic patients were significantly more likely to have had previous polyp surgery (chi‐square test: P < 0.05). Areas of intense eosinophilia were identified in all samples. There was a significant greater degree of activated eosinophilia in the asthmatic patients (t‐test: P < 0.05). Conclusions: We have demonstrated a higher number of previous operations in asthmatic patients, and also a greater degree of activated eosinophilia in asthmatic polyps compared with non‐asthmatics. This would suggest that eosinophil activity has a role to play in the pathogenesis of nasal polyps.     

三种促炎因子在鼻息肉及术后两周紧邻术区鼻黏膜的变化

目的 研究鼻息肉及鼻内镜术后2周紧邻术区鼻黏膜中血管细胞黏附分子（vascular cell adhesion molecule，VCAM）-1、嗜酸粒细胞亲合素（Eotaxin）及血管内皮生长因子（vascular endothelial growth factor，VEGF）的表达及相关性，探讨鼻息肉术后复发的可能机制。方法 应用链霉亲和素-过氧化物酶（SABC）免疫组化法检测30例鼻息肉及其中22例鼻内镜术后2周患者紧邻术区鼻黏膜的VCAM-1、eotaxin和VEGF的表达情况；HE染色光镜下观察组织结构、炎性细胞浸润情况。结果 ①HE染色可见鼻息肉组织嗜酸粒细胞大量浸润，术后则明显减少（t=2．891，P〈0．05）；②VCAM-1在鼻息肉手术前后均呈阳性表达，阳性面积差异无统计学意义（t=-2．051，P〉0．05），平均吸光度术后减弱（t=3．670，P=0．05）；Eotaxin手术前后阳性面积差异无统计学意义（t=0．739，P〉0．05），平均吸光度术后明显减弱（t=4．428，P〈0．05），Eotaxin术后腺体阳性率明显增加（t=-2．899，P〈0．05）；③VEGF阳性面积及平均吸光度手术前后表达差异均无统计学意义（t值分别为-0．037、0．825，P值均〉0．05）。结论 ①鼻息肉鼻内镜手术后嗜酸粒细胞数量明显减少，说明紧邻术区水肿状组织不同于鼻息肉。②VCAM-1、Eotaxin术后紧邻术区鼻黏膜阳性表达，说明Eotaxin有可能上调VCAM-1在血管内皮的表达，促进嗜酸粒细胞黏附于内皮细胞，穿内皮细胞问隙迁移到组织中，可能是息肉复发的基础。其中Eotaxin术后腺体阳性表达明显增加，推测其可能在鼻息肉复发早期发挥重要作用。③VEGF术后高表达，提示VEGF可促进术区血管增生及通透性增强，使局部组织增生、水肿，从而可能成为息肉复发过程中的重要因素之一。     

鼻息肉中血管内皮生长因子和碱性成纤维细胞生长因子的表达

目的探讨血管内皮生长因子 (vascular endothelial growth factor,VEGF)和碱性成纤维细胞生长因子 (basic fibroblast growth factor,bFGF)在鼻息肉发病过程中的意义。方法将鼻息肉患者分为A、B2组,A组为Ⅰ型及Ⅱ型1、2期鼻息肉患者,B组为Ⅱ型3期及Ⅲ型鼻息肉患者,采用免疫组化SP法对2组39例鼻息肉患者鼻息肉组织中VEGF、bFGF的表达进行检测。结果正常鼻粘膜中VEGF、bFGF的染色呈阴性,而在A、B组鼻息肉组织中的阳性率分别达到59%、41%和71%、80%,B组中阳性率和阳性细胞数均高于A组;VEGF和bFGF在鼻息肉组织中主要定位于基底膜周围的炎性细胞和上皮细胞以及血管周围和血管壁内皮细胞。结论 VEGF、bFGF通过在鼻息肉组织中的过度表达,促进息肉组织内的血管增殖和炎性细胞聚积,促进鼻息肉的发生发展,可能是鼻息肉病区别于鼻息肉的重要组织学特征之一。     

鼻息肉中血管内皮生长因子mRNA的检测与意义

目的 :检测鼻息肉组织和鼾症下鼻甲粘膜组织中的血管内皮生长因子 (VEGF) m RN A水平的表达 ,了解其在慢性炎症过程中的作用。方法 :取 6例行下鼻甲切除术的下鼻甲粘膜和 7例鼻息肉切除术的鼻息肉标本 ,用半定量的反转录 -聚合酶链反应 (RT- PCR)方法检测 VEGF的 m RNA表达。结果 :RT- PCR结果显示在鼻息肉组织中 V EGF的表达较鼾症患者下鼻甲粘膜组织明显升高。结论 :鼻息肉组织中 VEGF的表达显著升高 ,推测 VEGF在鼻息肉的形成、生长及复发过程中具有极其重要的作用。     

血管内皮生长因子在鼻息肉组织中的表达和意义

目的探讨血管内皮生长因子(vascular endothelial growth factor, VEGF)在鼻息肉组织中的表达及其在鼻息肉发病中的意义。方法将鼻息肉患者分为A、B 组,A组为Ⅱ型1、2期患者,B组为Ⅱ型3期及Ⅲ型患者。另有20例鼻中隔偏曲患者的正常下鼻甲组织作对照组。采用免疫组化SP法检测三组VEGF的表达。结果正常鼻黏膜中VEGF的染色呈弱阳性,而在A、B组鼻息肉组织中VEGF的阳性率明显高于对照组,B组中阳性率和阳性细胞数均高于A组;VEGF在鼻息肉组织中主要定位于基底膜周围的炎性细胞和上皮细胞以及腺体、血管周围和血管壁内皮细胞。结论VEGF通过在鼻息肉组织中过度表达促进息肉组织内的血管增殖和炎性细胞聚积,促进鼻息肉的发生发展。     

神经生长因子及其受体在鼻息肉中的表达及意义

目的 探讨神经生长因子(nerve growth factor,NGF)及其受体在鼻息肉组织中的表达。方法 采用免疫组化ABC法,检测20例鼻息肉组织(鼻息肉组)及6例正常下鼻甲黏膜(对照组)中NGF及其受体的表达。结果 对照组：正常下鼻甲黏膜中NGF及其受体的表达呈阴性;鼻息肉组：其黏膜上皮层和黏膜下层中NGF染色阳性率分别是90%(18/20)和95%(19/20);在鼻息肉组织同样位置发现了NGF的高亲和性受体TrKA(Tyrosine kinase A)高表达,在纤毛上皮细胞和腺上皮细胞中发现了NGF的低亲和性受体P75高表达。结论 NGF在鼻息肉组织中具有高表达特征,表明NGF在鼻息肉发生发展机制中发挥着重要作用。     

Immunohistochemical demonstration and semi-quantitation of vascular endothelial growth factor in recurrent versus non-recurrent nasal polyps

Objective The expression of some growth factors in nasal polyps has been examined, although investigations addressing the reason for recurrence in some patients are lacking. Vascular endothelial growth factor (VEGF) is expressed by inflammatory cells, as well as by endothelial and epithelial cells of nasal polyps. To determine whether VEGF may play a role in the recurrence of nasal polyps, we aimed to compare VEGF expression in recurrent versus non-recurrent polyps. In addition, expression in polyps from asthmatic patients was compared with that in polyps from non-asthmatics.

Material and Methods A total of 30 patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at enrolment in the long-term follow-up study. Fifteen patients had only 1 polypectomy (non-recurrence group; median observation period 81 months) and 15 had a median of 6.4 polypectomies (multiple recurrence group; median observation period 108 months). Five of 10 patients with asthma belonged to the non-recurrence group and 5 to the recurrence group. The polyp obtained at the initial polypectomy was examined for expression of VEGF by immunohistochemistry, using a polyclonal antibody. A blinded semi-quantitation and comparison of the intensity of immunolabelling were performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics.

Results VEGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of the vessel endothelium and some stromal mono- and polymorphonuclear leukocytes. Semi-quantitation of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics.

Conclusion Our findings indicate that the level of immunohistochemical expression of VEGF in recurrent and non-recurrent nasal polyposis is equivalent. Thus, the level of VEGF expression cannot predict a subsequent recurrence. The expression of VEGF is not upregulated in patients with asthma. Further studies are needed to determine the role of VEGF in nasal polyposis, with special reference to different stages of polyp formation, vascularization and growth.     

HLA antigens,nasal polyps and asthma

HLA antigens, nasal polyps and asthma HLA typing has been performed on a selected series of 29 patients with nasal polyps, with or without asthma. Despite the small series there was a significant increase in the haplotype A1/B8 in patients with both nasal polyps and asthma. No association was found in those with polyps alone. However, those with both conditions, who were positive for A1/B8, had more severe polyp disease. Three out of 4 patients with nasal polyps, asthma and sensitivity to aspirin were positive for A1/B8. In patients with nasal polyps, tissue typing might be of use in predicting both those who are most at risk of developing asthma, and also those who are most likely to have severe polyp disease. The association of A1/B8 with severe polyp disease and asthma, may imply that abnormalities of immune response are likely to be associated with the pathogenesis of both conditions.     

白细胞介素 25与白细胞介素 13及血管 内皮生长因子在鼻息肉组织中的表达

目的通过观察慢性鼻-鼻窦炎伴有鼻息肉（CRSw NP）患者鼻息肉组织中白细胞介素 25（interleukin 25,IL 25）、白细胞介素 13（interleukin 13,IL 13）和血管内皮生长因子（vascular endothelial growth factor,VEGF）的表达及分布,来探讨其在鼻息肉发病中的作用及三者的相关性。方法选取30例在鼻内镜下行手术治疗的慢性鼻-鼻窦炎伴有鼻息肉患者鼻息肉组织作为实验组,同期选取30例因鼻中隔偏曲而行下鼻甲部分切除患者的下鼻甲黏膜组织作为对照组。应用免疫组织化学SP法来检测两组鼻黏膜组织中IL 25、IL 13及VEGF的表达情况,并采用直线相关分析和χ2检验进行统计学分析。结果免疫组化结果显示,IL 25、IL 13及VEGF在鼻息肉组织中的阳性细胞计数分别为（21.0±12.08、23.94±18.23、19.13±9.85）,均高于对照组（4.19±2.54、7.67±2.02、3.44±1.52）,两两比较差异均具有统计学意义（P<0.05）;3个因子在鼻息肉组织中的表达两两均呈正相关性（P<0.01）。结论IL 25、IL 13及VEGF在鼻息肉组织中的表达均升高,在鼻息肉的发病中可能起重要作用;鼻息肉组织中IL 25、IL 13及VEGF的表达两两均呈正相关,提示细胞因子之间的相互作用对鼻息肉发生起促进作用;以细胞因子及其受体为靶点,可能对开拓治疗鼻息肉的新方法提供理论依据。     

缺氧对鼻息肉上皮细胞表达血管内皮生长因子的影响

目的　通过上皮细胞对缺氧和炎性因子刺激的主动应答作用 ,探讨上皮细胞和缺氧对鼻息肉早期形成的影响。方法　将鼻息肉及下鼻甲的上皮细胞分别在常氧和缺氧状态下 ,以及不同炎性因子刺激条件下进行无血清原代上皮细胞的培养 ,采用原位杂交 ,酶联免疫吸附测定 (enzyme linkedimmunosorbentassay ,ELISA)的方法 ,用促红细胞生成素 (erythropoietin ,EPO)为缺氧标志 ,检测上皮细胞分泌合成的血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)的线粒体RNA(mitochondriaRNA ,mRNA)和蛋白质水平的变化。结果　①缺氧条件下 ,EPO在来自于鼻息肉和下鼻甲的上皮细胞中明显表达 ,且两者无明显差异 ,表明EPO可作为组织缺氧标志 ;②上皮细胞合成的VEGFmRNA的能力在各种刺激下增加 ,而以缺氧条件下增加最为明显 (P <0 0 0 1) ,其中鼻息肉的合成能力要强于下鼻甲 (P <0 0 1) ;③VEGF的蛋白质表达水平在不同的炎性因子以及缺氧刺激下表达增加 (P <0 0 1) ,且随作用时间的延长而增强。其中以缺氧刺激下升高最为明显 (P <0 0 0 1)。鼻息肉的表达明显高于下鼻甲 (P <0 0 1)。结论　上皮细胞在缺氧时可主动合成VEGF。而这种中鼻道黏膜缺氧诱导的VEGF的产生和分泌是鼻息肉早期形成的重要机制。这也可能是鼻息     

Serum vascular endothelial growth factor in patients with head and neck squamous cell carcinoma

Vascular endothelial growth factor (VEGF) is a key pro-angiogenic cytokine expressed by most human tumours. Two isoforms, VEGF₁₂₁ and VEGF₁₆₅, are soluble and can be assayed in serum. Serum VEGF has been shown to be significantly raised in patients with solid tumours and shows some promise as a potentially useful tumour marker. Serum levels of VEGF were assayed in 52 patients with untreated head and neck squamous cell carcinoma (HNSCC) and 104 healthy controls. Serum VEGF is significantly raised in patients with HNSCC (P < 0.001), but there was no association with either tumour stage or specifically the presence of nodal metastases. Sixteen patients (31%) had a higher serum VEGF than 95th centile of controls, suggesting that serum VEGF measurement is of little practical use as an initial diagnostic tool. The finding that patients with HNSCC have significantly raised serum VEGF probably relates to enhanced platelet aggregation in these patients.     

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（ｖａｓｃｕｌａｒｐｅｒｍｅａｂｉｌｉｔｙｆａｃｔｏｒ，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对鼻息肉发生过程中组织极度水肿的产生可能有非常重要的作用。