Allergen extracts directly mobilize and activate human eosinophils

Allergic diseases are characterized by the presence of eosinophils, which are recruited to the affected tissues by chemoattractants produced by T cells, mast cells and epithelium. Our objective was to evaluate if allergens can directly activate human eosinophils. The capacity of purified allergen extracts to elicit eosinophil chemotaxis, respiratory burst, degranulation and up-regulation of the adhesion molecule complement receptor 3 (CR3) was determined in eosinophils isolated from healthy blood donors. Eosinophils stimulated with an extract from house dust mite (HDM) released the granule protein major basic protein (MBP) and up-regulated the surface expression of CR3. Cat allergen extracts also induced the up-regulation of CR3, but not the release of MBP; instead cat, as well as birch and grass allergens, elicited the release of eosinophil peroxidase (EPO). In addition, grass pollen extract caused the secretion of MBP. None of the allergens stimulated eosinophilic cationic protein release, nor production of free oxygen radicals. Both HDM and birch extracts were chemotactic for eosinophils. These findings establish that common aeroallergens can directly activate eosinophils in vitro. We propose that eosinophil activation in vivo is not exclusively mediated by cytokines and chemokines of the allergic inflammatory reaction, but could partly be the result of direct interaction between allergens and eosinophils.     

Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide

To clarify the essential role of NKT cells in allergy, we investigated the contribution of NKT cells to the pathogenesis of eosinophilic airway inflammation using alpha-galactosylceramide (alpha-GalCer), a selective ligand for NKT cells. Although continuous administration of alpha-GalCer during ovalbumin (OVA) sensitization increased OVA-specific IgE levels and worsened eosinophil inflammation, a single administration of alpha-GalCer at the time of OVA challenge completely prevented eosinophilic infiltration in wild-type mice. This inhibitory effect of alpha-GalCer was associated with a decrease in airway hyperresponsiveness, an increase in IFN-gamma, and decreases in IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluids. Analysis of lung lymphocytes revealed that production of IFN-gamma increased in NK cells, but not in T or NKT cells, following alpha-GalCer administration. Induction of vascular cell adhesion molecule-1 in the lungs of wild-type mice was also significantly attenuated by treatment with alpha-GalCer. These effects of alpha-GalCer were abrogated in J alpha281-/- mice, which lack NKT cells, and in wild-type mice treated with anti-IFN-gamma Ab. Hence, our data indicate that alpha-GalCer suppresses allergen-induced eosinophilic airway inflammation, possibly by inducing a Th1 bias that results in inhibition of eosinophil adhesion to the lung vessels.     

37℃凝血温度下正常人和哮喘患者血清ECP水平的测定

室温（２０℃）是广泛接受的血清ＥＣＰ测定凝血温度，但存在一些问题。设想体温３７℃可能是血清ＥＣＰ测定的有效凝血温度。为此，对６８例急性发作的哮喘患者在３７℃凝血温度下血清ＥＣＰ水平进行分析，比较凝血温度分别为２０℃和３７℃时同一患者血样本的ＥＣＰ水平变化，结果发现３７℃下哮喘患者血清ＥＣＰ水平（５０．９±３．１８μｇ／Ｌ）显著高于正常对照（１７．２７±１．３６μｇ／Ｌ，Ｐ＜０．０１）。在６８例病人中，３７℃凝血下有２８人血清ＥＣＰ水平高于正常值，而２０℃凝血下只有１７人血清ＥＣＰ水平高于正常值，两者间存在显著差异（Ｐ＜０．０５）。３７℃凝血温度下血清ＥＣＰ水平与哮喘症状计分显著相关（ｒ＝０．７７，Ｐ＜０．０１）。此外，尚测定了３７℃凝血温度下１０１位１０～５０岁的健康人血清ＥＣＰ水平，结果显示３７℃下正常人血清ＥＣＰ水平的几何均数是１７．８１μｇ／Ｌ，血清ＥＣＰ水平的正常值为７０μｇ／Ｌ以下（９５％的可信限）。本研究表明，在血清ＥＣＰ的测定中设凝血温度为３７℃不仅是有效、简化的方法，而且还可减少哮喘患者血清ＥＣＰ水平的假阴性。     

白三烯受体拮抗剂对哮喘局部免疫影响的实验研究

目的为研究白三烯(LTs)拮抗剂安可来(Accolate)对哮喘大鼠气道嗜酸性粒细胞(EOS)、淋巴细胞(Lym)浸润以及T细胞活化表达白细胞介素-2受体(IL-2R)的影响,探讨安可来治疗哮喘的作用机制.方法应用卵清蛋白腹腔注射致敏和反复超声雾化吸入激发诱喘建立大鼠哮喘模型.随机分为正常对照组(A组)、阳性对照组(B组)、预防治疗组(C组)和治疗组(D组).A组以生理盐水致敏和激发,B、C、D组建立哮喘模型.C组自激发诱喘前1周起预防性给予安可来饲喂,诱喘期继续治疗.D组自激发日起行安可来饲喂.病理切片观察大鼠支气管壁EOS、Lym浸润,ABC法检测大鼠T细胞IL-2R的表达.结果正常对照组大鼠支气管壁可见少量Lym浸润但无明显EOS浸润和炎症反应,IL-2R阳性细胞数目很少.阳性对照组支气管壁EOS、Lym浸润以及IL-2R阳性细胞数目明显增多,较正常对照组有显著差异(P＜0.01).饲喂安可来预防和(或)治疗能减少支气管壁EOS、Lym浸润以及IL-2R阳性细胞数目,与阳性对照组相比有显著差异(P＜0.05).结论安可来能减轻哮喘大鼠肺组织炎症反应,抑制EOS、Lym等炎症细胞向气道组织的浸润,对大鼠T细胞活化表达IL-2R亦有明显抑制作用.     

变应性鼻炎与气道高反应的关系

目的 :探讨变应性鼻炎与气道高反应性的相关性。方法 :用 1∶ 1 0 0 ( w/v)蒿属花粉对 50例变应性鼻炎和 2 0例正常者做支气管激发试验 ,分别测定两组第 1秒用力呼气量 ( FEV1) ;测血清中嗜酸性粒细胞阳离子蛋白 ( ECP)。结果 :支气管激发试验前 ,两组支气管均无症状 ,鼻炎组FEV1为 ( 70± 2 0 ) % ,对照组为 ( 85.6± 8.9) % ,两组有显著性差异 ( P <0 .0 1 ) ;支气管激发后 ,鼻炎组中 2 3例胸部有紧迫感 ,1 0例有哮鸣 ,5例有喘息 ,1 2例无症状 ,激发阳性率为 76%。对照组均无支气管症状。激发后鼻炎组 FEV1为 ( 60± 2 0 ) % ,对照组为 ( 85.6± 8.9) % ,两组有显著性差异 ( P <0 .0 5)。鼻炎组 ECP为 ( 30 .37± 1 8.92 ) μg/L,对照组为 ( 5.2 4± 3.2 3) μg/L,两组有显著性差异 ( P <0 .0 5)。结论 :变应性鼻炎不仅鼻粘膜有变态反应所致的慢性炎症 ,而且大部分气道也有慢性炎症反应而导致气道高反应性。     

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。     

变异性心绞痛患者血管内皮功能相关指标测定的临床意义

目的研究变异性心绞痛(VAP)患者血管内皮功能相关指标的变化。方法征集疑为冠状动脉性心脏病(CAD)或电生理研究提示心律失常而行诊断性心导管术的住院患者共93例,根据相关诊断标准将其分为3组,其中 VAP 患者39例,劳力性心绞痛(EAP)患者35例,对照组19例。根据临床症状的严重度,将 VAP组再分为轻度 VAP 组22例和重度 VAP 组17例。采集血样分别测定各组患者的白细胞(WBC)及分类计数、血浆纤维蛋白原(Fbg)、内皮素(ET-1)、血管性血友病因子(vWF)、C-反应蛋白(CRP)以及冠心病(CHD)其他危险因子,如总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)等的变化。结果除 EAP 组高密度脂蛋白胆固醇(HDL-C)明显低于对照组外(P<0.01)。其他CHD 危险因子、体温、WBC 总数、CRP 等在 VAP、EAP 及对照组间差异无显著性意义(P>0.05)。而重度 VAP组 EOS 明显高于其他三组(P<0.01)。重度 VAP 组血浆 Fbg、ET-1和 vWF 也明显高于其他3组(P<0.05)。VAP 患者经药物治疗后,EOS 计数、血浆 Fbg、ET-1和 vWF 明显低于对照组(P<0.01)。结论 EOS 计数和血浆 Fbg,ET-1和 vWF 水平可预示 VAP 病情严重度,提示冠状动脉痉挛可能引起 EOS 和 Fbg、ET-1和 vWF 水平升高。