Basic fibroblast growth factor in nasal polyps immunohistochemical and quantitative findings

Basic fibroblast growth factor (bFGF) is a mediator with potent mitogenic properties. Increased amounts of this mediator have been demonstrated in damaged lung tissue, and it has been suggested to increase the healing of gastro-duodenal ulcers. In order to quantify the amounts and document the localization of bFGF in nasal polyps, polyp tissue from 12 patients undergoing polypectomy was analyzed by ELISA and immunohistochemistry. Mucosa from the inferior turbinate was analyzed in the same manner for comparison. The amount of bFGF detected in polyp tissue was significantly higher than that in turbinate mucosa. The amount of bFGF was also significantly higher in the group of patients with high degree of inflammation. The immunohistochemical findings demonstrated abundant bFGF activity mainly in the glandular acini, in the epithelium, in infiltrating inflammatory cells and in the vessel walls. We propose that bFGF may contribute in a significant way to the formation of nasal polyps.     

Basic fibroblast growth factor expression in recurrent versus non-recurrent nasal polyposis

Various growth factors are expressed in nasal polyps, and some of these have been suggested to play a role in polyp formation. A potential relation between growth factor expression and polyp recurrence, however, is undetermined. Basic fibroblast growth factor (bFGF) is expressed in mononuclear cells, as well as in endothelial and epithelial surface and gland cells of nasal polyps. To determine whether bFGF may play a role in the recurrence of nasal polyps, the present study aimed at a comparison of bFGF expression in recurrent versus non-recurrent polyps. Further, the expression in polyps from asthmatic patients was compared with that from non-asthmatics. Thirty patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at entry to the long-term follow-up study. Fifteen patients only had one polypectomy (no recurrence group, with a median observation time of 81 months). Fifteen patients had a median of 6.4 polypectomies (multiple recurrence group, with a median observation time of 108 months). Five of nine patients with asthma belonged to the non-recurrence group and four to the recurrence group. The polyp from the entrance polypectomy was examined for expression of bFGF by immunohistochemistry, using a polyclonal antibody. A masked semi-quantification of staining intensity was performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics. bFGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of some mononuclear cells and some fibroblast-like cell profiles in the polyp stroma. Vascular endothelium was labeled occasionally. Semi-quantification of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics. We conclude that the level of immunohistochemical expression of bFGF in recurrent and non-recurrent nasal polyposis is equivalent. Thus, the level of bFGF expression in the primary polyp can not predict a subsequent recurrence. The expression of bFGF is not up-regulated in patients with asthma. Further studies are needed to determine a potential role of bFGF in nasal polyposis, with special reference to different stages of polyp formation and growth.     

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。     

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.     

The effect of topical corticosteroid on basic fibroblast growth factor in nasal polyp tissue

BACKGROUND: The etiology of nasal polyposis and pathophysiological mechanisms of polyp formation is still poorly understood. Experimental models have suggested that nasal polyp growth requires extracellular matrix formation and is associated with fibroblast proliferation. Intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. Basic fibroblast growth factor (bFGF) is a potent angiogenesis factor and is mitogenic for a wide range of cell types. We investigated the alteration of bFGF levels in nasal polyp tissue after administration of topical corticosteroid. METHODS: Nasal polyp tissues were obtained from 36 patients with diffuse nasal polyposis before and after topical nasal steroid treatment. As a topical nasal steroid mometasone furoate was given for 4 weeks in a dosage of 200 microg/day. The bFGF levels were measured by competitive enzyme immunoassay method. RESULTS: The mean levels of tissue bFGF, before and after topical nasal steroid treatment, were 1485 +/- 826 ng/mg protein (range, 416-3434 ng/mg) and 1340 +/- 749 ng/mg protein (range, 330-3288 ng/mg), respectively. The levels of bFGF in nasal polyps were significantly lower than those before treatment after administration of topical nasal steroid (p = 0.011). CONCLUSION: Administration of topical nasal steroid decreases bFGF levels of nasal polyp. It may be suggested that one of the effects in diminishing the size of nasal polyps is by decreasing the bFGF.     

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.     

Significance and expression of transforming growth factor beta in human nasal polyp tissue]

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of transforming growth factor beta (TGF-beta) in human inflammatory nasal polyps. METHODS: TGF-beta 1-3 in nasal polyp tissues and inferior turbinate mucosa of twenty-five polyposis patients were detected with immunohistochemistry alkaline phosphatase and anti-alkaline phosphatase (APAAP) method. The inferior turbinate mucosa of eight healthy volunteers were selected as control. Six polyp tissues were estimated with double immunolabeling and Western-blot analysis to compare the characterization of the TGF-beta isoforms expression and the proportion of macrophages and eosinophils in nasal polyp tissues. RESULTS: The expression of TGF-beta 1-3 in nasal polyps was significantly higher than that in nasal mucosa and indetecable in nasal mucosa from healthy volunteers; TGF-beta 1 was the main isoform detected in nasal polyps; TGF-beta positively was accompanied by numerous macrophage and eosinophil infiltration. CONCLUSIONS: TGF-beta mainly TGF-beta 1 is strongly expressed in nasal polyps and its mucosa, where it could be produced by macrophages and eosinophils. TGF-beta could induce modification of epithelium and connective tissue and therefore be involved in the pathogenesis of nasal polyposis.     

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。     

Decreased connexin 43 expression correlated with eosinophil infiltration in nasal polyps

BACKGROUND: A nasal polyp usually is characterized by eosinophil infiltration. Eosinophil-fibroblast interaction is an important event of persistent inflammation in airways. We have found abundant connexin 43 (Cx43) expression in subepithelial fibroblasts of nasal mucosa. Thus, we aim to analyze the relationship of Cx43 expression and eosinophil in nasal polyps. METHODS: In 25 nasal polyps and 19 inferior turbinates, indirect immunofluorescent and hematoxylin and eosin staining were performed in adjacent sections. We calculated the density of Cx43 staining and eosinophil individually by fluorescent and light microscope. RESULTS: Positive Cx43 staining under confocal microscope was shown as punctated spots on cell margin. The density of Cx43 and eosinophil staining was significantly different between groups of inferior turbinate and nasal polyp (p = 0.01 and 0.03, respectively). Decreased Cx43 expression in the subepithelial fibroblast was correlated with eosinophil infiltration in nasal polyps. Spearman rank order coefficient was equal to -0.43 (p < 0.05). CONCLUSION: This is the first demonstration of decreased Cx43 expression related to eosinophil infiltration. To the best of our knowledge, interleukin-8 may be a link between Cx43 and eosinophil and orchestrating both in developing nasal polyps.     

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.     

Expressions of vascular endothelial growth factor and basic fibroblast growth factor in nasal polyp and its role]

OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor(bFGF) in the pathophysiology of nasal polyp. METHODS: Thirty-nine patients with nasal polyp were divided into two groups: group A(representing type 1 and type 2 phase 1-2) and group B (representing type 2 phase 3 and type 3). The expression of VEGF and and bFGF in both groups were studied with immunohistochemical method. RESULTS: VEGF and bFGF were not detected in norms. The detection rates of VEGF and bFGF were 59%, 41%, and 71%, 80% in group A and group B respectively. The positive rate and the number of positive cells were higher significantly in group B than that in group A. VEGF and bFGF were located mainly in the inflammatory cells and epithelial cells around the basilar membrane and inflammatory cells and endothelial cells around the vessel. CONCLUSIONS: The overexpression of VEGF and bFGF in nasal polyp may contribute to the growth of vessels, accumulation of inflammatory cells, as a result, to enhance the development of nasal polyposis. This phenomenon maybe an important histological mark distinguishing ordinary polyp from polyposis.     

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。