肾透明细胞癌中Eotaxin-1的表达与肿瘤增殖能力相关

目的探讨嗜酸性粒细胞趋化因子-1 Eotaxin-1在肾透明细胞癌(ccRCC)中的表达情况及其与肿瘤增殖能力的关系。方法免疫组织化学检测58例肾透明细胞癌患者肾癌组织及癌旁组织中Eotaxin-1以及增殖细胞核抗原(PCNA)的表达并分析其与肾癌临床病理特征的关系;用Western blot法分析10例相互配对肾癌组织、癌旁组织中Eotaxin-1及PCNA的表达,并对Eotaxin-1与PCNA做相关性分析。结果 Eotaxin-1主要表达于胞质,PCNA主要表达于细胞核内,Eotaxin-1和PCNA在肾癌组织的阳性率明显高于癌旁组织(P0.05);病理分级为2-3级组的Eotaxin-1及PCNA阳性率显著高于病理分级1级组(P0.01)。临床分期为Ⅲ/Ⅳ组的Eotaxin-1及PCNA阳性率显著高于临床分期Ⅰ/Ⅱ组(P0.05),有淋巴结转移组的Eotaxin-1及PCNA阳性率高于无淋巴结转移组(P0.05);10例肾癌组织中Eotaxin-1及PCNA蛋白水平显著高于癌旁组织(P0.01,P0.05);Eotaxin-1与PCNA在肾癌组织中的表达存在相关性(P0.05)。结论肾透明细胞癌组织中Eotaxin-1与肾透明细胞癌的增殖能力密切相关,对Eotaxin-1的研究可能为临床对肾透明细胞癌诊断治疗提供新的思路。     

骨髓与支气管哮喘嗜酸性粒细胞增多症的关系研究进展

产生于骨髓的嗜酸性粒细胞(Eos)在哮喘气道炎症中发挥重要作用.骨髓的造血机制构成了哮喘气道炎症形成过程的活性组分,如骨髓嗜酸性粒细胞及其祖细胞数量的增加;骨髓细胞表达致炎因子如IL-5 mRNA、蛋白质和IL-5受体等.治疗哮喘的药物如糖皮质激素能抑制骨髓嗜酸性粒细胞形成.骨髓和肺组织一样,可能成为抗哮喘治疗的另一重要靶器官.     

嗜酸性粒细胞活化趋化因子与支气管哮喘的研究进展

嗜酸性粒细胞活化趋化因子(Eotaxin)是CC趋化因子家族成员之一,由结构性细胞和渗出性炎症细胞产生,是嗜酸性粒细胞、嗜碱性粒细胞和Th2型细胞因子的化学激活趋化剂,通过其受体(CCR3)选择性地诱导嗜酸性粒细胞在肺内黏附、募集和脱颗粒。     

磷酸化丝/苏氨酸蛋白激酶B在小鼠过敏性气道反应肺组织炎性细胞中的差异表达

目的:探讨丝/苏氨酸蛋白激酶B(Akt)在过敏性小鼠肺组织不同炎性细胞中的活化状况.方法:应用卵蛋白致敏激发BALB/c小鼠制备过敏性气道炎症反应模型,抽取肺泡灌洗液(BALF)进行细胞总数计数和不同炎性细胞分类计数,应用免疫组织化学检测磷酸化Akt(p-Akt)在过敏性小鼠肺组织中不同炎性细胞的表达.结果:过敏性小鼠BALF中总细胞数明显高于正常鼠;分类细胞计数中,正常组以巨噬细胞为主,而过敏性小鼠的嗜酸性粒细胞、淋巴细胞百分比明显升高;免疫组织化学显示p-Akt在过敏性小鼠气道中嗜酸性粒细胞中表达明显高于淋巴细胞和巨噬细胞,而在淋巴细胞中表达明显高于巨噬细胞.结论:Akt在过敏性小鼠的气道炎症中的作用与炎性细胞的种类密切相关,发挥不同的诱导嗜酸性粒细胞和巨噬细胞增多、趋化、释放炎性细胞因子和对抗淋巴细胞凋亡等重要的作用.     

抗白介素5单克隆抗体抑制哮喘小鼠嗜酸性粒细胞迁移

目的 观察抗白介素5(IL-5)单克隆抗体对哮喘小鼠嗜酸性粒细胞(Eos)从骨髓到气道迁移的影响.方法 15只雄性C57BL/6小鼠.常规法复制哮喘,并在每次卵白蛋白(Ova)激发前2 h鼻腔内滴入抗IL-5单克隆抗体,同时设立阴性对照组,即以生理盐水代替Ova 和抗IL-5抗体.在末次抗原激发后12 h测定支气管肺泡灌洗液(BALF)、外周血(PB)和骨髓(BM)中炎症细胞数以及肺组织内Eos数.结果 Ova抗原激发后12 h小鼠的BALF、PB和BM及细支气管和肺组织中的Eos数显著增加(P＜0.01, P＜0.05).抗IL-5单克隆抗体则使上述变化显著减轻(P＜0.05,P＜0.01).结论 抗IL-5单克隆抗体能显著抑制哮喘小鼠嗜酸性粒细胞的迁移.     

支气管哮喘患者血清骨桥蛋白和嗜酸细胞趋化因子表达及临床意义

支气管哮喘是慢性气道炎症性疾病,嗜酸性粒细胞在气道炎症反应中起重要作用[1]。现认为细胞因子网络失衡是发病的基础,而Th2细胞因子、嗜酸细胞趋化因子(eotaxin)共同诱导的嗜酸性粒细胞募     

骨髓与支气管哮喘嗜酸性粒体细胞增多症的关系研究进展

产生于骨髓的嗜酸性粒细胞（Eos)在哮喘气道炎症中发挥重要作用。骨髓的造血机构成了哮喘气道炎症形成过程的活性组分，如骨髓嗜酸性粒细胞及其祖细胞数量的增加；骨髓细胞表达致炎因子如IL－5mRNA、蛋白质和IL－5受体等。治疗哮喘的药物如糖皮质激素能抑制骨髓嗜酸性粒细胞形成。骨髓和肺组织一样，可能成为抗哮喘治疗的另一种重要靶器官.     

地塞米松对体外不同密度嗜酸性粒细胞凋亡及Fas mRNA表达的影响

哮喘患者低密度嗜酸性粒细胞(Eos)被认为是活化了的Eos。地塞米松(DM)对不同密度Eos凋亡的影响，研究很少。本研究用DM干预哮喘豚鼠体外不同密度的Eos，以原位杂交方法观察Fas mRNA的表达，TUNEL法检测Eos凋亡，以了解DM促进不同密度Eos凋亡的机制。     

过敏性紫癜患者血液嗜酸性粒细胞IL-18和IL-18受体表达升高

目的探讨过敏性紫癜患者血液嗜酸性粒细胞中IL-18、IL-18受体(IL-18 receptor,IL-18R)和IL-18结合蛋白(IL-18 binding protein,IL-18BP)的表达,并分析其相关性。方法收集过敏性紫癜患者的外周静脉血,用蒿草花粉、尘螨和梧桐花粉过敏原粗提液刺激,流式细胞术检测血液中嗜酸性粒细胞IL-18、IL-18R、IL-18BP的表达,并用SPSS分析其相关性。结果过敏性紫癜患者IL-18+和IL-18R+细胞的比例分别升高了1.83倍(P=0.048)和1.12倍(P=0.025),而IL-18BP+嗜酸性粒细胞的平均荧光强度(mean fluorescence intensity,MFI)降低了30%(P=0.005)。过敏性紫癜患者IL-18+和IL-18R+嗜酸性粒细胞的比例呈中度相关(相关系数r=0.559,P=0.000)。此外,梧桐花粉过敏原粗提液诱导过敏性紫癜患者血液IL-18+嗜酸性粒细胞的MFI升高了37%(P=0.027)。结论过敏性紫癜患者嗜酸性粒细胞中IL-18和IL-18R表达上调而IL-18BP表达下调,提示嗜酸性粒细胞表达的IL-18、IL-18BP和IL-18R可能在过敏性紫癜中起重要作用。     

地塞米松对哮喘豚鼠嗜酸细胞凋亡及bc1-2 mRNA表达的影响

目的观察地塞米松(DM)对哮喘豚鼠体外不同密度的嗜酸性粒细胞(Eos)凋亡及bc1-2表达的影响, 并探讨激素促进哮喘Eos凋亡的机制.方法以卵蛋白激发哮喘豚鼠模型48 h后, 进行支气管肺泡灌洗, 分离灌洗液中不同密度的Eos.加入DM(10 10～10 5mol/L),以原位杂交法检测Eos的bc1-2表达, TUNEL法检测Eos的凋亡.结果 DM干预24 h,可见Eos凋亡增加,bc1-2 mRNA表达降低,且呈剂量依赖性.bc1-2mRNA的表达与Eos凋亡呈负相关.结论 DM可抑制bc1-2的表达,促进Eos凋亡.bc1-2表达的减少可能是DM调节Eos凋亡的机制之一.     

Mechanisms and regulation of polymorphonuclear leukocyte and eosinophil adherence to human airway epithelial cells.

Polymorphonuclear leukocytes (PMN) and eosinophils (Eos) are important cellular participants in a variety of acute and chronic inflammatory reactions in the airway. Histologic evidence has implicated direct interactions between these two subsets of leukocytes and airway epithelial cells during inflammation. A comprehensive characterization and comparison of physiologic stimuli and adhesion molecule involvement in granulocyte-epithelial-cell interactions done with nontransformed human airway epithelial cells has not been reported. We therefore examined the regulation and biochemical mechanisms governing granulocyte-epithelial-cell adhesion, using either purified PMN or Eos and primary cultures of human bronchial epithelial cells (HBECs). We investigated the involvement of a number of proinflammatory signals associated with allergic and nonallergic airway inflammation, as well as the contribution of several epithelial and leukocyte adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and members of the beta(1), beta(2), and beta(7) integrin families. ICAM-1 was expressed at low levels on cultured HBECs and was markedly upregulated after stimulation with interferon (IFN)-gamma or, to a lesser extent, with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1. VCAM-1 was not present on resting HBECs, and was not upregulated after stimulation with IFN-gamma, IL-1, IL-4, or TNF-alpha. PMN adhesion to HBECs could be induced either through activation of PMN with IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), or C5a, but not with IL-5 or by preactivation of HBECs with TNF-alpha or IFN-gamma. Blocking antibody studies indicated that PMN-HBEC adherence depended on beta(2) integrins, primarily alpha(M)beta(2) (Mac-1). Adherence of Eos to HBECs could be induced through activation of Eos with IL-5, GM-CSF, or C5a, but not with IL-8 or by prior activation of HBECs with TNF-alpha of IFN-gamma. Maximal adhesion of Eos and PMN required pretreatment of HBECs with either TNF-alpha or IFN-gamma in addition to leukocyte activation. Adherence of Eos to unstimulated HBECs was mediated through both beta(1) and beta(2) integrins, whereas adhesion of Eos to activated HBECs was dominated by beta(2) integrins. Adhesion of both Eos and PMN was inhibited by treatment of HBECs with blocking antibodies to ICAM-1. Differential utilization of beta(1) and beta(2) integrins by Eos, depending on the activation state of the epithelium, is a novel finding and may affect activation and/or recruitment of Eos in airway tissue. Mechanisms of adhesion of HBECs to Eos and PMN, as evidenced by the different responsiveness of the two latter types of cells to IL-8 and IL-5, may account for a prevalence of Eos over PMN in certain airway diseases.     

Flagellin Alleviates Airway Allergic Response by Stabilizing Eosinophils through Modulating Oxidative Stress

Eosinophil (Eo) degranulation plays a central role in the initiations of allergic attacks. Flagellin (FGN), the major component of bacterial flagella, has immune regulatory functions. This study aims to investigate the role of FGN in alleviating the allergic reaction by stabilizing Eos. A toll-like receptor 5-knockout mouse strain was employed to test the role of FGN in stabilizing Eos. An airway allergy mouse model was developed to test the administration of FGN in alleviating the airway allergy by stabilizing Eos. The results showed that FGN was required in stabilizing Eos in the airway tissues. FGN prevented specific antigen-induced Eo activation. Oxidative stress was associated with the antigen-induced Eo activation that could be counteracted by the presence of FGN. The FGN levels were lower and chymase levels were higher in the airway tissues of mice with allergic inflammation. Negative correlation was detected between the data of FGN and chymase in the lung tissues. Chymase physically contacted FGN to speed up its degradation. The administration of FGN alleviated experimental allergic inflammation in the mouse airways by stabilized Eos in the lung tissues. In conclusion, FGN contributes to Eo stabilization. The administration of FGN alleviates the experimental airway allergy. The data suggest that FGN can be a candidate to be employed in the treatment of allergic disorders.     

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.     

Nasal lavage fluid concentrations of eotaxin-1 (CCL11) in naturally occurring allergic rhinitis: relationship to disease activity, nasal luminal eosinophil influx, and plasma protein exudation

BaCKGROUND: Eotaxin-1 (CCL11) is a CC chemokine whose nasal eosinophilic chemotactic activity in vivo and in vitro has been demonstrated primarily using nasal allergen challenge models. The extension of these challenge findings to the in vivo setting has been limited. OBJECTIVE: To obtain nasal lavage fluid from volunteers with perennial and seasonal (in- and out-of-season) allergic rhinitis (AR) and non-atopic non-rhinitic controls for the measurement of eotaxin-1 concentrations and to relate these findings to the symptomatic disease severity, the percentage of lavage eosinophils, and to alpha(2)-macroglobulin (alpha(2)-MG) lavage concentrations, as a marker of vascular permeability and an index of airway inflammation. METHODS: Thirty-seven volunteers with AR (16 seasonal and 21 perennial) and 20 non-atopic non-rhinitic volunteers were recruited and phenotyped. Nasal lavage fluid was obtained by standardized protocol. The nasal lavage fluid concentrations of eotaxin and alpha(2)-MG were measured by ELISA, and differential cell counts performed on cytospins. RESULTS: Eotaxin-1 nasal lavage fluid concentrations were significantly higher in both the perennial and seasonal (in-season) AR groups compared with the controls, and significantly related to the severity of symptom expression and to the percentage of lavage eosinophils. The lavage eosinophil counts were significantly higher in both the symptomatic rhinitis groups compared with the control groups and correlated with the lavage concentrations of alpha(2)-MG. alpha(2)-MG levels were significantly increased in seasonal (in-season) rhinitics compared with both non-atopic controls and seasonal (out-of-season) rhinitics. A significant correlation was observed between the levels of alpha(2)-MG and levels of eotaxin in the symptomatic allergic rhinitic groups. CONCLUSIONS: This study clearly demonstrates the relevance of eotaxin-1 to the pathogenesis of naturally occurring AR.     

Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4-stimulated epithelial cells

Epithelial cells play an important role in orchestrating mucosal immune responses. In allergic-type inflammation, epithelial cells control the recruitment of eosinophils into the mucosa. Th2-type cytokine-driven release of eosinophil-active chemokines from epithelial cells directs eosinophil migration into the mucosal epithelium. CCR3, the main eosinophil chemokine receptor, regulates this process; however, the respective contribution of individual CCR3 ligands in eosinophil transepithelial migration is less well understood. Using an in vitro transepithelial chemotaxis system, we found that eotaxin-3 produced by IL-4-stimulated airway epithelial cells and CCR3 on eosinophils exclusively mediate eosinophil transepithelial migration. Eotaxin-3 protein levels were also increased in the nasal mucosal epithelium recovered from allergic patients as compared to non-allergic patients. Surprisingly, eotaxin-3 in IL-4-stimulated airway epithelial cells was predominantly cell surface bound, and the cell surface form was critical for eosinophil transepithelial migration. Eotaxin-3 cell surface association was partially glycosaminoglycan (GAG) dependent, but was completely protein dependent, suggesting that eotaxin-3 associates with both GAG and cell surface proteins. We thus provide evidence that cell surface-associated eotaxin-3 is the critical IL-4-dependent chemotactic signal mediating eosinophil transepithelial migration in the setting of allergic inflammation.     

地塞米松对哮喘豚鼠嗜酸细胞凋亡及bcl—2 mRNA表达的影响

目的 观察地塞米松（DM）对哮喘豚鼠体外不同密度的嗜酸性粒细胞（Eos)凋亡及bcl-2表达的影响，并探讨激素促进哮喘Eos凋亡的机制。方法 以卵蛋白激发哮喘豚鼠模型48h后，进行支气管肺泡灌洗，分离灌洗液中不同密度的Eos。加入DM（10^10-10^5mol/L），以原位杂交法检测Eos的bcl-2表达，TUNEL法检测Eos的凋亡。结果 DM干预24h，可见Eos凋亡增加，bcl-2 mRNA表达降低，且呈剂量依赖性。bcl-2 mRNA的表达与Eos凋亡呈负相关。结论 DM可抑制bcl-2的表达，促进Eos凋亡。bcl-2表达的减少可能是DM调节Eos凋亡的机制之一。     

类风湿性关节炎患者Eotaxin-3 +2497基因多态性研究

目的:研究类风湿性关节炎(RA)患者Eotaxin-3 +2497T/G单核苷酸多态性(SNP)。方法:用聚合酶链反应方法对目的基因进行扩增,用单链构象多态性方法进行SNP分析,最后用测序及四引物聚合酶链反应方法对结果进行验证。结果:RA组与对照组Eotaxin-3 +2497位存在TT和TG两种基因型,且基因型分布符合Hardy-Weinberg平衡定律;RA组与对照组Eotaxin-3 +2497位基因型频率及等位基因频率间差异有显著性意义(P<0.05)。结论:RA患者Eotaxin-3 +2497位G等位基因频率明显高于对照组。     

Sublingual immunotherapy: the optimism and the issues

The acceptability of sublingual immunotherapy (SLIT) in guidelines or statements has recently increased. SLIT is currently used in Europe, Asia, and Australia for the treatment of allergic respiratory diseases. Four meta-analyses have shown that SLIT is an effective tool for the treatment of patients with asthma and/or rhinitis, and only conflicting results were reported for children with allergic rhinitis. Moreover, it offers logistic advantages and is safe. However, some unmet needs are to be faced, such as the difficulty of manufacturers to achieve the homogeneity of standardized vaccines, the magnitude of their clinical efficacy, and the pivotal question of an early intervention with SLIT in young children with IgE-mediated disorders. Altogether, SLIT has already given convincing results in respiratory diseases both in adults and children. In the future, this route of administration of allergic vaccines may improve even the treatment of patients with IgE-mediated food allergy. These patients indeed deserve better than allergen avoidance. The immunomodulatory treatment of allergic diseases probably has found a new tool; however, a more balanced understanding of this form of allergen immunotherapy is needed. This aim could be achieved through: (1) the improvement of products standardization quality; (2) an attempt to modify in children the natural course of allergic diseases; and (3) new research on mechanisms of action.