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。     

黏附分子在实验性变应性鼻炎鼻黏膜中的表达

变应性鼻炎迟发相反应阶段是以嗜酸粒细胞为代表的大量的炎性细胞的浸润而导致的慢性炎症，血管细胞黏附分子-1(vascular cell adhesion molecule-1，VCAM-1)、细胞间黏附分子-1(intercellular adhesion molecule-1，ICAM-1)在嗜酸粒细胞等炎性细胞的黏附、浸润到黏膜炎症区域起着重要作用。本研究观察实验性变应性鼻炎鼻黏膜中黏附分子的表达。     

变应性鼻炎整合素的表达及其与肥大细胞的关系

变应性鼻炎(allergic rhinitis，AR)属于Ⅰ型超敏反应，肥大细胞是其发病的主要启动细胞之一。有学者认为肥大细胞的迁移、聚集、定位很可能受到整合素α4β1及其配体血管细胞间黏附分子-1(vascular cell adhesion molecule，VCAM-1)的影响。本研究目的在于探讨AR患者鼻黏膜中整合素α4β1及其配体VCAM-1的表达及其与肥大细胞的关系。     

血管细胞黏附分子-1及P-选择素在喉咽癌中的表达及与微血管密度的相关性研究

目的：检测喉咽癌组织中血管细胞黏附分子-1（vascular cell adhesion molecule-1，VCAM-1）及P-选择素的表达及其与微血管密度（mierovessel density，MVD）间的关系，探讨VCAM-1及P选择素在喉咽癌血管生成中的意义。方法：用免疫组织化学方法检测40例喉咽癌组织和10例正常口咽部黏膜组织中VCAM-1、P选择素及CD34表达并计数MVD。结果：VCAM-1及P-选择素在喉咽癌组织中的表达率显著高于正常口咽部黏膜组织（P〈0．01）；喉咽癌组织的MVD值显著高于正常口咽部黏膜组织（P〈O．01），MVD值与有无淋巴结转移密切相关（P〈0．01）；VCAM-1及P-选择素表达阳性组MVD值显著高于表达阴性组（P〈0．01），且VCAM-1及P-选择素表达均与MVD呈正相关（P〈0．05）；在喉咽癌淋巴结转移组中，VCAM-1及P选择素的表达呈正相关关系。结论：VCAM-1及P-选择素在喉咽癌组织中的高表达在肿瘤的浸润和转移中起重要作用，并与肿瘤血管生成有关．     

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。     

E-选择素在鼻息肉中的分泌与表达

目的:检测黏附分子E选择素在鼻息肉中的分泌水平与表达部位,借以探讨其与鼻息肉可能的病理机制的相关性。方法:采用酶联免疫吸附测定法检测25例鼻息肉(鼻息肉组)组织匀浆中E选择素水平,以9例鼻中隔手术患者之代偿肥大的下鼻甲后端黏膜作为对照(对照组);同时对上述标本进行苏木精伊红染色及E选择素免疫组织化学染色,观察其表达情况。结果:鼻息肉组大量嗜酸粒细胞浸润。E选择素浓度为(42.58±13.52)μg/L,对照组为(11.35±3.17)μg/L,差异有统计学意义(P<0.01)。E选择素主要表达于血管内皮、腺体上皮、间质和浸润炎症细胞上。鼻息肉组腺体上皮阳性表达率为92.0%,对照组为55.6%,差异有统计学意义(P<0.05)。鼻息肉组在血管内皮上阳性表达率为84.0%,对照组为44.4%;鼻息肉组在间质及浸润炎症细胞阳性表达率为92.0%,对照组为33.3%,差异均有统计学意义。Spearman相关性分析E选择素在血管内皮上的表达和在间质及浸润炎症细胞上的表达呈正相关(r=0.544,P<0.01)。结论:高表达的E选择素可能通过参与嗜酸粒细胞等炎症细胞的浸润、活化、增殖,从而在鼻息肉的形成过程中起重要作用。     

Fas配体和细胞黏附分子1在肥大扁桃体组织高内皮小静脉中的表达及意义

目的：探讨Fas配体（FasL）和细胞黏附分子1（ICAM-1）在肥大扁桃体组织高内皮小静脉（HEV）中的表达及意义。方法：收集37例扁桃体切除标本,其中20例为慢性肥大性扁桃体炎患者（CHT组）,17例为特异性扁桃体肥大患者（ITH组）。应用苏木精-伊红染色法和免疫组织化学染色（SABC法）研究2组扁桃体组织HEV的T、B淋巴细胞的数目,内皮细胞中FasL及ICAM-1的表达。结果：CHT组HEV中ICAM-1的表达明显高于ITH组（P〈0.05）,而ITH组HEV中FasL的表达明显高于CHT组（P〈0.05）。结论：HEV内皮细胞表达的ICAM-1和FasL均可能在扁桃体肥大的发生、发展过程中起一定的促进作用,前者主要促进CHT发展,后者主要导致ITH。     

两种细胞粘附分子及肿瘤坏死因子-α在鼻息肉组织中的表达及意义

目的 :通过检测鼻息肉组织中细胞间粘附分子 (ICAM- 1) ,血管细胞粘附分子 (VCAM- 1)及肿瘤坏死因子(TNF-α)的表达 ,以了解三者与嗜酸性粒细胞浸润的关系 ,探讨粘附分子与 TNF-α的相关性。方法 :分别以 ICAM- 1、VCAM- 1及 TNF-α的单克隆抗体对 4 2例鼻息肉组织 (鼻息肉组 )和 16例鼻甲粘膜 (对照组 )进行免疫组织化学染色 ,光镜观察。结果 :ICAM- 1、VCAM- 1及 TNF-α在鼻息肉组织中的表达均明显高于对照组 (P <0 .0 1) ,ICAM- 1、VCAM- 1与 TNF-α的表达呈正相关 (r1 =0 .5 2 ,p1 <0 .0 1;r2 =0 .6 8,p2 <0 .0 1)。鼻息肉中两种细胞粘附分子与嗜酸性粒细胞浸润程度一致。结论 :1嗜酸性粒细胞在鼻息肉的发生发展中发挥重要作用 ;2而 TNF-α通过上调鼻息肉组织内皮细胞ICAM- 1及 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、聚集于组织局部 ,引起鼻息肉形成。     

鼻息肉中细胞间黏附分子1和E-选择素的表达及意义

鼻息肉是耳鼻咽喉科常见病,严重危害人们身心健康。鼻息肉发病机制至今仍未完全阐明,众多研究表明嗜酸性粒细胞（eosinophils,Eos）浸润是鼻息肉最显著的病理特征。因此,探讨以Eos为代表的炎性细胞聚集和活化成为研究鼻息肉发病机制的热点。本文拟通过分析鼻息肉组织中细胞间黏附分子1（intercellular adhesion molecule-1,ICAM．1）、E-选择素的表达，探讨其与Eos浸润及鼻息肉形成的关系。     

细胞因子和细胞黏附分子在慢性鼻窦炎中的表达及意义

目的探讨细胞因子和细胞黏附分子在慢性鼻窦炎发病机制中的作用.方法应用免疫组化SABC法检测两型慢性鼻窦炎患者上颌窦黏膜内白细胞介素-1(IL-1)、IL-8、干扰素-γ(IFN-γ)和粒细胞巨噬细胞集落刺激因子(GM-CSF)以及细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1).结果在慢性单纯性鼻窦炎Ⅰ型组中IL-1,IL-8阳性细胞数明显高于对照组(P<0.01),而Ⅱ型组中IL-8,IFN-γ和GM-CSF表达明显高于对照组(P<0.01),Ⅰ型组IL-1明显高于Ⅱ型组(P<0.01).ICAM-1的表达两组鼻窦炎无明显差异,而明显高于对照组(P<0.01),VCAM-1各组表达均较少,无明显差异.结论细胞因子及ICAM-1在慢性鼻窦炎发病中起一定的作用.通过对不同细胞因子类型及黏附分子的研究可进一步了解慢性鼻窦炎的发病机制.     

Soluble adhesion molecules in middle ear effusions from patients with chronic otitis media with effusion

Soluble forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been identified in the peripheral blood and other body fluids. These soluble adhesion molecules have been reported to reflect the upregulation of cell surface ICAM-1 and VCAM-1 expression in inflammatory diseases. The levels of soluble ICAM-1 and soluble VCAM-1 in 37 middle ear effusions from 37 patients with chronic otitis media with effusion (OME) were quantitatively determined with enzyme-linked immunosorbent assays. The levels of soluble ICAM-1 in mucoid effusions were significantly higher than those in serous effusions, but the levels of soluble VCAM-1 did not differ significantly between the two types of effusion. The levels of soluble VCAM-1 in effusions from atopic patients were significantly higher than those from non-atopic patients, whereas the levels of soluble ICAM-1 in samples from atopic patients were significantly lower than those from non-atopic patients. Therefore, our data suggest that an increase in soluble VCAM-1 plays a more important role in the pathogenesis of OME in atopic patients than in non-atopic patients. In addition, soluble ICAM-1 is likely to play a more important role in the pathogenesis of OME in nonatopic patients than soluble VCAM-1.     

Expression of Adhesion Molecules in Nonallergic Chronic Sinusitis

Endothelial and epithelial adhesion molecules are important in the recruitment of leukocytes to inflammatory sites. To determine the relationship between recruited leukocytes and adhesion molecules in the paranasal sinus mucosa of nonallergic chronic sinusitis, we surgically obtained mucosa from 16 patients and identified the expression of intercellular adhesion molecules(ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin by immunohistochemistry. Neutrophils were significantly dominant in the nasal discharge as compared with eosinophils. The degree of neutrophil infiltration in the paranasal sinus mucosa was prominent in both intraepithelial and subepithelial areas as compared with the lamina propria. In each tissue site, the degree of infiltration of neutrophils was similar to that of eosinophils. These findings suggest that the tissue neutrophils actively and rapidly migrated into the lumen. All the adhesion molecules except VCAM-1 were expressed in the vascular endothelial cells. On the other hand, the surface epithelial cells showed the expression of only ICAM-1. The expression of ICAM-1 on the endothelial cells correlated with the degree of neutrophil infiltration in the mucosa. The eosinophil infiltration was not dependent on any adhesion molecules examined here. It was concluded that ICAM-1 expression in the mucosa may be involved in neutrophil recruitment and may contribute to the establishment of the inflammatory cell distribution in the paranasal sinus of nonallergic chronic sinusitis.     

细胞黏附分子及一氧化氮合酶在变应性鼻炎鼻黏膜中的表达

目的:对细胞黏附分子(CAM)及一氧化氮合酶(NOS)进行原位观察,探讨它们在变应性鼻炎(AR)发病中的作用。方法:采用链霉卵白素-生物素复合体(SABC)法,对AR患者及对照组手术切除的下鼻甲黏膜内细胞间黏附分子-1(ICAM-1)、血管CAM-1(VCAM-1)和淋巴细胞功能相关抗原-1(LFA-1),以及神经型NOS(nNOS)、诱导型NOS(iNOS)和内皮细胞型NOS(eNOS)进行原位检测。结果:AR下鼻甲黏膜内3种CAM表达的阳性细胞数ICAM-1为[(14.4±2.2)个/HP(×400),以下同],LFA-1为(17.2±3.3)个/HP,VCAM-1为(11.5±2.7)个/HP;对照组下鼻甲黏膜内3种CAM表达的阳性细胞数ICAM-1为(8.7±1.8)个/HP,LFA-1为(10.3±2.1)个/HP,VCAM-1为(6.9±1.8)个/HP。t值分别是11.57,10.02和8.07(均P<0.01)。AR及对照组下鼻甲黏膜内nNOS表达的阳性细胞数分别为(9.4±1.7)个/HP和(4.7±1.3)个/HP,t值为12.62,(P<0.01);iNOS表达的阳性细胞数分别为(27.5±3.2)个/HP和(4.3±1.7)个/HP,t值为36.03(P<0.01)。eNOS表达的阳性细胞数分别为(6.5±2.1)个/HP,(6.2±1.9)个/HP,t值为0.62(P>0.05)。结论:CAM在黏膜上皮、腺上皮、血管内皮以及黏膜下的各种炎性细胞等的表达,说明CAM参与AR的发生、发展。nNOS和iNOS在AR的发病过程中可能起重要作用。     

Relationship Between Infiltrating Cells and Adhesion Molecules in the Nasal Mucosa of Patients with Allergic Rhinitis

Antigen-induced changes of cell adhesion molecules and their relationships to infiltrating cells were investigated immunohistochemically in nasal mucosa of perennial allergic rhinitis patients. An increased expression of E-selectin and VCAM-1 was noted on the vascular endothelium of the nasal mucosa 15-25 h after the topical antigen challenge. Although there was no increased expression of ICAM-1, we noted a positive correlation between the expression of E-selectin and ICAM-1. The expression of E-selectin and VCAM-1 as well as ICAM-1 was revealed to be correlated with the number of EG2-positive cells and CD4-positive cells, but not with elastase-positive cells. These findings suggest that all these adhesion molecules play a role in the topical influxes of eosinophils and CD4-positive cells in allergic nasal mucosa.     

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。     

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     

Topical budesonide treatment reduces endothelial expression of intercellular adhesion molecules (vascular cell adhesion molecule-1 and P-selectin) and eosinophil infiltration in nasal polyps.

Infiltration of eosinophil granulocytes and endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and P-selectin was investigated in biopsies of polyps and inferior turbinates from 16 patients with nasal polyps, by the use of immunohistochemical staining and stereological quantification before, during and after topical treatment with budesonide (Rhinocort Turbuhaler). Before glucocorticoid treatment a higher density of eosinophil profiles (p < 0.005), making up a larger proportion of the total cellular infiltrate (p < 0.0005), was found in the polyps compared with the inferior turbinates. Endothelial VCAM-1 expression was higher in polyps than in inferior turbinates (p < 0.005), in contrast with the expression of P-selectin, which was more frequently expressed in the inferior turbinates (p < 0.05). Topical glucocorticoid treatment reduced the density of eosinophil profiles (p < 0.05) and the endothelial expression of VCAM-1 (p < 0.007) and P-selectin (p < 0.02) in polyps. Eosinophil counts and VCAM-1 expression returned to pre-treatment levels 8 weeks after discontinuation of budesonide treatment. The observed reduction in endothelial expression of cellular adhesion molecules may interfere with cellular recruitment in nasal polyps and thus contribute to the known anti-inflammatory effect of glucocorticoid in nasal polyposis.     

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.     

Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa

The factors involved in the development of chronic inflammation and edema in nasal polyps remain to be clarified. The expression of vascular endothelial growth factor (VEGF) has been described in plasma cells, suggesting that plasma cells may play a major role in the development of edema in nasal polyps through the production of VEGF. We performed immunohistochemical analysis using specific antibodies to VEGF and to the known VEGF receptors, VEGFR-1 and VEGFR-2, on paraffin sections of human nasal polyps ( n=11) and controls of human mucosa of the normal middle turbinates ( n=6). In normal turbinate mucosa, sporadic immunostaining for VEGF was observed throughout the endothelial cells of the small veins and arteries. VEGFR-1 and VEGFR-2 expression was faint in the healthy turbinates. In nasal polyp tissues, strong immunostaining for VEGF was found in the endothelium of blood vessels and in the infiltrating perivascular inflammatory cells. Fibroblasts also stained for VEGF. Strong immunolabeling to VEGFR-1 was evident in the vascular endothelium, whereas weak to moderate VEGFR-1-staining was generally confined to scattered mononuclear round cells. Mononuclear round cells and the endothelium of capillaries revealed immunoreactivity to VEGFR-2. These findings support a role for VEGF and its receptors, VEGFR-1 and VEGFR-2, in the development and perpetuation of edema and angiogenesis in nasal polyps.