急性非淋巴细胞白血病P-糖蛋白表达及排出活性检测的临床意义

目的探讨成人初治急性非淋巴细胞白血病（ＡＮＬＬ）Ｐ糖蛋白（Ｐｇｐ）表达及罗丹明１２３排出活性（Ｒ１２３Ｅ）与预后的关系。方法流式细胞术检测ＡＮＬＬ白血病细胞Ｒ１２３Ｅ及Ｐｇｐ表达。结果Ｒ１２３Ｅ＋率及Ｐｇｐ＋率分别为３９５％及３４２％。Ｍ３的Ｒ１２３Ｅ＋率（０／６）明显低于其他亚型（４３８％）（Ｐ＜００５）。Ｐｇｐ表达与活性存在明显相关性（Ｐ＜０００１），７８９％的患者表达与活性一致（１０例Ｐｇｐ＋Ｅ＋，２０例Ｐｇｐ－Ｅ－）；２１１％存在表达与活性分离（３例Ｐｇｐ＋Ｅ－，５例Ｐｇｐ－Ｅ＋），Ｐｇｐ－Ｅ＋提示非Ｐｇｐ介导的排出活性在ＡＮＬＬ耐药中可能具有重要作用。Ｒ１２３Ｅ＋完全缓解（ＣＲ）率（２／１１，１８２％）及Ｐｇｐ＋者的ＣＲ率（２／１０，２０％），明显低于Ｒ１２３Ｅ－的９２９％（１３／１４）及Ｐｇｐ－的８６７％（１３／１５）（Ｐ分别＜００１及＜０００１）。结论Ｐｇｐ表达及活性检测在成人ＡＮＬＬ中均具有重要的预后意义     

巨细胞病毒感染与动脉粥样硬化的临床研究

目的探讨人类巨细胞病毒（ＨＣＭＶ）感染、肿瘤坏死因子（ＴＮＦ）及血浆内皮素（ＥＴ）浓度与动脉粥样硬化的关系。方法采用间接免疫荧光技术测定急性心肌梗塞组（２０例）、冠状动脉狭窄组（２０例）及正常对照组（３０例）血清人类巨细胞病毒抗体，用放射免疫法测定血清ＴＮＦ及ＥＴ的浓度。结果急性心肌梗塞组ＨＣＭＶＩｇＭ阳性１４例（７０％），ＨＣＭＶＩｇＧ阳性２０例（１００％），ＨＣＭＶＩｇＭ、ＩｇＧ双阳性１４例（７０％）；冠状动脉狭窄组ＨＣＭＶＩｇＭ阳性１９例（９５％），ＨＣＭＶＩｇＧ阳性１９例（９５％），ＩｇＭ、ＩｇＧ双阳性１８例（９０％）；正常对照组ＨＣＭＶＩｇＭ阳性６例（２０％），ＨＣＭＶＩｇＧ阳性２６例（８２％），ＩｇＭ、ＩｇＧ双阳性６例（２０％），与正常对照组比较，差异有显著性（Ｐ＜０００１，Ｐ＜００５，Ｐ＜０００１）；冠心病急性心肌梗塞组、冠状动脉狭窄组与正常对照组相比，血清ＴＮＦ、血浆ＥＴ显著增高（Ｐ＜０００１）。结论患者的ＨＣＭＶ感染、内皮细胞受损和ＴＮＦ作用可能参与了冠心病发生发展的过程。     

~(131)I抗AFP抗体-MMC双弹头导向治疗肝癌31例

目的观察化疗兼内照射的新型双弹头免疫导向治疗肝癌的疗效．方法以马抗人ＡＦＰ多克隆抗体（抗ＡＦＰＡｂ）和大鼠抗人ＡＦＰ单克隆抗体（抗ＡＦＰＭｃＡｂ）为载体，核素１３１Ｉ和丝裂霉素（ＭＭＣ）为双弹头，采用改良氯胺Ｔ法制备１３１Ｉ抗ＡＦＰＭｃＡｂＭＭＣ（双弹头１）和１３１Ｉ抗ＡＦＰＡｂＭＭＣ（双弹头２），静脉滴注，每月１次，治疗不能切除中晚肝癌３１例（治疗组）．治疗１，２，３次分别占４，１７和１０例，放射剂量（ＭＢｑ／例）均值依次为１９３５１±３７７４，６５１９±２３２４和９９２０±２３０５．结果治后肿瘤缩小率、血清ＡＦＰ下降率和１，２年生存率分别高于同期经动脉插管灌注（ＴＡＩ）或化疗栓塞（ＴＡＣＥ）的对照组（５００％，１５／３０比３００％，９／３０Ｐ＜００５；６６７％，１８／２７比２８０％，７／２５Ｐ＜００１和５００％比３３０％，３４０％比３３％Ｐ＜００１），治疗组病例的进展率（１００％）明显低于对照组（４００％，Ｐ＜００１）．结论双弹头疗效提高，由于抗体、核素１３１Ｉ和抗癌药的协同作用而增强了对癌细胞的杀伤力所致．     

类风湿关节炎病人血清细胞因子水平以及与炎症指标的相关性

目的：进一步研究细胞因子在类风湿关节炎（ＲＡ）中的作用以及与疾病的关系。方法：随机就诊的７２名门诊及住院ＲＡ病人红细胞沉降率（ＥＳＲ）、Ｃ反应蛋白（ＣＲＰ）以及细胞因子白细胞介素１α（ＩＬ１α）、ＩＬ１β、ＩＬ２、ＩＬ６、肿瘤坏死因子α（ＴＮＦα）、粒细胞单核细胞集落刺激因子（ＧＭＣＳＦ）被测定。全部数据用于ＲＡ病人细胞因子水平的研究，并对细胞因子与炎症指标的相关性进行探讨。结果：ＲＡ病人血清ＧＭＣＳＦ、ＴＮＦα水平较健康对照组明显增高（Ｐ＜０００１）。ＩＬ６、ＧＭＣＳＦ与炎性指标ＥＳＲ（ｒ＝０２６，Ｐ＜００１；ｒ＝０２８，Ｐ＜００２）和ＣＲＰ（ｒ＝０４０，Ｐ＜００００１；ｒ＝０４７，Ｐ＜００００１）呈正相关。结论：ＲＡ病人血清ＩＬ６、ＧＭＣＳＦ、ＴＮＦα较其他细胞因子与ＲＡ疾病有更密切的相关性。细胞因子作为重要的免疫物质参与炎症反应在ＲＡ的病理过程中起到了重要作用。     

慢性阻塞性肺疾病和肺心病患者血液动力学与循环内皮细胞变化

目的探讨慢性阻塞性肺疾病（ＣＯＰＤ）和肺心病时血循环内皮细胞、血液动力学的变化及意义。方法运用右心导管检查技术和血循环内皮细胞（ＣＥＣ）分离技术，用硫巴比妥法及羟胺法测定血丙二醛（ＭＤＡ）及超氧化物岐化酶（ＳＯＤ）。结果肺心病组肺动脉平均压［（ｍＰＡＰ）３７６±０７５ｋＰａ、血ＣＥＣ数量每０９微升为１６７０±２６５与ＣＯＰＤ组（８４８±２２３）比较，差异有显著性（Ｐ＜０．０１），血ＣＥＣ数量与动脉血氧分压（ＰａＯ２）比较呈显著负相关（ｒ＝０．９４２３，Ｐ＜０．００１），血ＣＥＣ数量与肺动脉压比较呈显著正相关（ｒ＝０．８２７０，Ｐ＜０．００１），肺心病组丙二醛（ＭＤＡ）、超氧化物歧化酶（ＳＯＤ）与ＣＯＰＤ组比较，差异有显著性（Ｐ＜０．０１）。结论缺氧可加重血管内皮细胞损伤     

消化系恶性肿瘤患者血清与腹水中细胞因子活性变化

目的研究消化系恶性肿瘤（ＤＭＴ）患者血清与腹水中内源性ＩＬ２,ＩＬ６,ＩＬ８,ＴＮＦα和ＩＦＮγ的生物学活性．方法应用ＥＬＩＳＡ法检测了１５例ＤＭＴ患者（肝癌１１例,胆总管癌１例,胰腺癌１例,胃癌１例,直肠癌１例）血清与腹水中５种细胞因子活性,并与６例肝硬变（ＬＣ）患者和８例正常成人进行了比较分析．结果ＤＭＴ患者血清ＩＬ２,ＩＬ６的生物学活性显著低于ＬＣ（Ｐ＜００５）;腹水中ＩＬ２,ＩＬ８活性显著低于ＬＣ组（Ｐ＜００１）,而ＩＬ６和ＩＦＮγ活性则高于ＬＣ组（Ｐ＜００１,００５）．ＤＭＴ患者血清中ＩＬ６,ＩＬ８活性明显高于正常成人组（Ｐ＜００５）;ＩＬ２,ＩＦＮγ则低于正常成人组,但缺乏显著性．肝癌血清和腹水中ＩＬ２活性显著高于非肝癌组（Ｐ＜００５）;而ＩＬ６活性则相对降低（Ｐ＜００５）．结论恶性肿瘤患者血清中ＩＬ２和ＩＦＮγ活性低于正常人,是ＤＭＴ患者抗肿瘤免疫功能缺陷的标志．ＩＬ６对于预测ＤＭＴ患者的预后具有重要的意义     

SLE 患者 PBMC 分泌IL-3 活性水平的初步研究

目的：为了研究ＳＬＥ患者ＰＢＭＣ分泌ＩＬ３的能力。方法：采用ＭＴＴ比色方法，用ＩＬ３依赖株（ＴＦ１）分别测定了１５例活动期、１５例缓解期ＳＬＥ患者和正常对照者ＰＢＭＣ培养上清中ＩＬ３的活性水平。结果：ＳＬＥ患者ＰＢＭＣ自发分泌ＩＬ３的活性水平显著高于正常人（Ｐ＜０００１），活动期和缓解期患者之间无显著性差异（Ｐ＞００５），经ＰＨＡ刺激后ＳＬＥ患者和正常人ＰＢＭＣ分泌ＩＬ３的活性水平均显著增加（Ｐ＜０００１），在ＳＬＥ病人中，以伴发显著血小板减少的５例患者ＰＢＭＣ分泌ＩＬ３的活性水平最低。结论：ＩＬ３可能参与ＳＬＥ的致病过程，且和ＳＬＥ患者血小板减少有关。     

风湿热活动性指标的初步探讨

目的：为了指导风湿热的防治并改善其预后，寻找特异性和敏感性较高的指标以探讨风湿热活动性。方法：采用最具生物活性的Ａ组链球菌壁多糖部分作包被抗原，以ＥＬＩＳＡ法测定抗链球菌壁多糖抗体（ＡＳＰ）ＩｇＧ、ＩｇＭ。结果：风湿性心脏病活动期ＡＳＰＩｇＧ、ＩｇＭ的水平（３６５２±２１９５和２６１９±０７４８）和阳性率（５６１％和７５６％）显著高于正常人、风湿性关节炎和风湿性心脏病静止期（Ｐ＜００５～００００１），后二者ＡＳＰ－ＩｇＧ、ＩｇＭ的水平和阳性率明显高于正常人（Ｐ＜００５～００１）；随治疗ＡＳＰ－ＩｇＭ下降较快（Ｐ＜０００１），ＡＳＰ－ＩｇＭ与反映风湿热活动的传统指标（血沉、Ｃ－反应蛋白等）之间具有正相关性，ＡＳＰ在风湿热活动中的阳性率（８５４％）明显高于ＥＳＲ、ＣＲＰ和ＡＣＬ。结论：ＡＳＰ在判断风湿热活动性方面具有较高的敏感性     

新霉素抑制促胃液素促人结肠癌细胞株SW480增殖的研究

目的观察新霉素（ＮＭ）对五肽促胃液素（ＰＧ）促人结肠癌细胞株ＳＷ４８０增殖的影响,探讨肌醇脂质信号通路可能参与的作用及临床意义．方法ＭＴＴ比色分析法检测活细胞数（ＶＣＣ）;［３Ｈ］肌醇标记细胞进行三磷酸肌醇（ＩＰ３）分析;Ｃａ２＋荧光测定技术检测细胞内Ｃａ２＋浓度;［γ３２Ｐ］ＡＴＰ掺入法测定蛋白激酶Ｃ（ＰＫＣ）活性．结果ＰＧ＋ＮＭ组的ＳＷ４８０细胞活细胞数降低,与对照组相比Ｐ＜００１,与ＰＧ组相比Ｐ＜００１;ＰＧ＋ＮＭ组细胞内ＩＰ３,Ｃａ２＋浓度降低,与ＰＧ组相比Ｐ＜００１,与对照组相比Ｐ＞００５;ＰＧ＋ＮＭ组膜ＰＫＣ活性降低,与ＰＧ组相比Ｐ＜００５,与对照组相比Ｐ＞００５．结论ＮＭ可能通过肌醇质脂信号通路而抑制ＰＧ促人结肠癌细胞株ＳＷ４８０的增殖,这将为结肠癌的抗信息传导治疗提供实验依据．     

哮喘患者痰液中亚硝酸盐/硝酸盐含量的变化及其意义

目的　探讨痰液中一氧化氮（ Ｎ Ｏ） 代谢终产物———亚硝酸盐／ 硝酸盐（ Ｎ Ｏ２／ Ｎ Ｏ３） 测定在哮喘临床中的应用价值。方法　应用 Ｇｒｉｅｓｓ 重氮法测定４５ 例不同时期、不同程度哮喘患者及１５ 例慢性支气管炎（ 慢支） 合并肺心病急性发作期患者痰液、血清 Ｎ Ｏ２／ Ｎ Ｏ３ 含量，同步测定哮喘患者痰液中嗜酸细胞阳离子蛋白（ Ｅ Ｃ Ｐ） 水平及肺通气功能。结果　哮喘轻、中、重度发作期患者痰液 Ｎ Ｏ２／ Ｎ Ｏ３ 中位数浓度（ 分别为１３１ μｍｏｌ／ Ｌ、１３６ μｍｏｌ／ Ｌ） 与缓解期组（８５ μｍｏｌ／ Ｌ） 及正常对照组（６３ μｍｏｌ／ Ｌ） 比较，差异有显著性（ Ｐ＜ ００５） ；发作期组与缓解期组比较差异有显著性（ Ｐ＜ ０ ．０５） ；慢支合并肺心病急性发作期患者痰液 Ｎ Ｏ２／ Ｎ Ｏ３ 水平（３３ μｍｏｌ／ Ｌ） 与各哮喘组及正常对照组比较，差异有显著性（ Ｐ＜ ００５） 。缓解期及发作期哮喘患者痰液 Ｎ Ｏ２／ Ｎ Ｏ３ 与一秒钟用力呼气容积占预计值百分比（ Ｆ Ｅ Ｖ１ 占预计值％ ）间呈显著负相关（ｒ 分别＝ － ０５８７ 、－ ０４８５ ， Ｐ 均＜ ００５） ；而痰液 Ｎ Ｏ２／ Ｎ Ｏ３ 与 Ｅ Ｃ Ｐ 间呈     

二氧化硫对慢性变应性气道炎症、气道上皮下纤维化的促进作用

目的 研究SO2所造成的急性气道炎症、上皮损伤对卵白蛋白反复激发致敏小鼠慢性变应性气道炎症、气道上皮下纤维化(subepithelial fibrosis,SEF)的影响.方法 吸入50 ppm SO2诱发急性气道炎症;卵白蛋白反复激发4、8周,观察首次激发前吸入、未吸入SO2的小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)细胞学、内皮素1(endothelin-1,ET-1)和转化生长因子β1(transforming growth factor-β1,TGF-β1)水平、肺组织羟脯氨酸(Hyp)含量、气道上皮基底膜下纤维面积及气道组织学改变.结果吸入SO2导致急性中性粒细胞性气道炎症、上皮损伤,卵白蛋白反复激发诱发慢性变应性气道炎症、SEF,二者均导致BALF中ET-1、TGF-β1水平增高.与同期单纯激发组相比,损伤激发组SEF出现更早,气道炎症、SEF更显著,肺组织Hyp与BALF中TGF-β1呈正相关.结论 预先吸入SO2导致的急性气道炎症、上皮损伤能加剧慢性变应性气道炎症,促进并加重SEF,可能与气道炎症、上皮损伤过程中气道微环境ET-1、TGF-β1表达上调有关.     

急性期和慢性期哮喘小鼠模型在哮喘致病过程中的对比研究

目的 比较卵清蛋白(ovalbumin,OVA)诱导的急性期和慢性期哮喘小鼠模型在气道炎症、气道重塑和气道高反应方面的差异,明确在哮喘致病过程中肺组织的病理变化.方法 48只BALB/c小鼠随机分为急性组和慢性组,其中急性组包括正常对照组(A1组)和急性哮喘组(A2组),慢性组包括正常对照组(B1组)和慢性哮喘组(B2组).OVA致敏和激发方法分别构建急性早期哮喘模型和慢性期哮喘模型后,测定气道阻力,BALF细胞计数和分类计数,酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测IL-4、IL-5、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和γ-干扰素(interferon-γ,IFN-γ).HE染色观察气道炎症,AB-PAS和Masson染色测定气道重塑.结果 与正常小鼠相比,A2组和B2组小鼠气道阻力均明显升高,但B2组小鼠气道阻力在基础值即发生明显改变.相比于慢性组哮喘小鼠,急性组哮喘小鼠BALF中细胞总数和嗜酸粒细胞数,IL-4、IL-5和IFN-γ水平,肺组织气道血管周围炎症细胞聚集,以及气道黏液分泌水平等炎症性改变更为明显.相比于A2组,B2组哮喘小鼠BALF中TGF-β1和VEGF水平,气道平滑肌增厚,上皮下胶原沉积,上皮下纤维化等改变更为显著.结论 在急性早期哮喘中主要是以炎症性改变为主,但在哮喘早期即开始出现轻度的重塑性改变;而在慢性期哮喘中虽然存在炎症性改变,但影响哮喘症状的因素却主要以器质性改变为主.     

A study on tumor necrosis factor alpha, macrophage inflammatory protein-2 and myeloperoxidase in blood, broncho-alveolar fluid and lung tissues of rat chronic bronchitis model

OBJECTIVE: To study the nature and mechanisms of airway inflammation in chronic bronchitis and observe the effects of inhaled glucocorticoids on inflammatory indices. METHODS: Rat chronic bronchitis model was established by intratracheal instillation of small dose of lipopolysaccharide (LPS, 1 g/L). Experiments were performed in 28 male Sprague-Dawley rats, which comprised four groups in random, i.e. chronic bronchitis model group, normal saline treated group, dexamethasone treated group and healthy control group. The levels of myeloperoxidase (MPO) of blood and lung tissues, and tumor necrosis factor (TNF)alpha and macrophage inflammatory protein-2 (MIP-2) of plasma, broncho-alveolar fluid (BALF) and lung tissues were determined by biochemical and ELISA methods. Total and differential white blood cell counts of BALFwere carried out. RESULTS: (1) The levels of TNFalpha and MIP-2 in BALF and lung tissues, and MPO in lung tissues of chronic bronchitis model group were significantly increased than those of control group (P < 0.05). (2) More significant increase in total white blood cell count and neutrophils in BALF was found in rat chronic bronchitis group than in control group (P < 0.001). (3) Significant positive correlations were observed between the level of MPO and MIP-2 of lung tissues, the level of MPO and TNFalpha of lung tissue and the total cell counts and the level of MIP-2 of BALF and lung tissue. (4) More significant decrease in total cell counts and neutrophils of BALF and levels of MPO in lung tissue was found in dexamethasone-treated group as compared to those of chronic bronchitis group. CONCLUSION: Recruitment and activation of neutrophils seem to be the characteristics of chronic bronchitis. TNFalpha and MIP-2 may be involved in the process of chemotaxis and activation in airway inflammation in chronic bronchitis. Inhaled steroids might have some effects on chronic bronchitis by limiting the airway inflammation.     

Relationship between antimicrobial proteins and airway inflammation and infection in cystic fibrosis

Antimicrobial proteins are important in lung defense and are potential therapeutic agents in chronic airways infection such as seen in cystic fibrosis (CF). In preparation for future clinical studies, we sought (1) to determine levels of three antimicrobial proteins [lactoferrin, lysozyme, and secretory leukoprotease inhibitor (SLPI)] in the CF airway and (2) to examine the relationships between these antimicrobial proteins and airway inflammation and infection. We examined bronchoalveolar lavage fluid (BALF) from 45 individuals with CF and 23 disease control individuals. Airway inflammation was measured through BALF neutrophil counts and neutrophil elastase activity. Infection was assessed through quantitative counts of CF‐related bacterial pathogens. BALF lysozyme activity and lactoferrin levels were elevated in individuals with CF compared to controls whereas SLPI levels were not different between the groups. Among the CF subjects, lysozyme activity and lactoferrin increased with age while SLPI decreased with age. Lysozyme activity and lactoferrin concentrations correlated positively with neutrophil counts but not with bacterial colony counts. SLPI levels were inversely related to both neutrophil counts and bacterial colony counts. This study provides information concerning the levels of antimicrobial proteins present in the CF airway that are relevant to future clinical trials of these compounds and demonstrates clear relationships between antimicrobial protein‐specific levels and airway inflammation and infection. Pediatr Pulmonol. 2009; 44:402–409. © 2009 Wiley‐Liss, Inc.     

Bronchoalveolar lavage fluid cytology reflects airway inflammation in beagle puppies with acute bronchiolitis.

Beagle puppies infected with both canine parainfluenza virus type 2 (CPI2) and Bordetella bronchiseptica (Bb) develop more severe acute bronchiolitis and airways hyperresponsiveness than do those infected with CPI2 or Bb alone. The aim of our study was to characterize the inflammatory response associated with airway hyperresponsiveness, and to determine whether the inflammatory cell response of bronchoalveolar lavage fluid (BALF) reflected changes in the bronchioles in this model. We investigated 25 beagle puppies (ages 76 +/- 5 days, mean +/- SEM) in four groups: controls (n = 6), or puppies inoculated with both CPI2 and Bb (CPI2-Bb) (n = 11), with only CPI2 (n = 4), or only Bb (n = 4). The puppies were killed 3-4 days after inoculation, the lungs excised, the intermediate lobe lavaged, and BALF and the bronchiolar wall tissue examined for neutrophils and other inflammatory cells. Control puppies had no evidence of inflammation. However, the CPI2-Bb puppies had developed cough and rhinitis, positive cultures for CPI2 and Bb, and a neutrophilic cellular response in both the bronchioles and the BALF. Puppies inoculated with only CPI2 or Bb had milder illnesses and no significant bronchiolar and BALF neutrophilic response. For all groups, the severity of bronchiolar wall inflammation correlated with the total number of BALF inflammatory cells, and bronchiolar wall neutrophil counts correlated with the percentage of neutrophils in the BALF. The illness and the airway hyperresponsiveness observed in the CPI2-Bb group were associated with airway neutrophilia. Our studies support the hypothesis that neutrophils are associated with airway dysfunction in this model, and the use of BALF to study the process.     

白介素17在慢性阻塞性肺疾病大鼠肺组织中的表达及与气道炎症及重塑的关系

目的 探讨白介素17(IL-17)在慢性阻塞性肺疾病(COPD)大鼠气道炎症及重塑中的作用.方法 采用被动吸烟80 d来制备大鼠COPD模型.支气管肺泡灌洗计数支气管肺泡灌洗液(BALF)中细胞计数和百分比;采用半定量图像分析法测量小气道管壁和平滑肌层厚度;免疫组织化学法检测肺组织IL-17的表达;酶联免疫吸附试验法检...     

Inhaled fluticasone propionate reduces concentration of Mycoplasma pneumoniae, inflammation, and bronchial hyperresponsiveness in lungs of mice

BACKGROUND: Mycoplasma pneumoniae has been shown to induce airway inflammation and bronchial hyperresponsiveness (BHR) in mice. Inhaled corticosteroids are the mainstay of asthma treatment, but their effects on M. pneumoniae and associated airway inflammation and BHR are poorly understood. METHODS: Four groups of mice were studied to determine whether inhaled fluticasone propionate (FP) could attenuate airway inflammation and BHR by reducing or eliminating M. pneumoniae in lungs. The active group received aerosolized FP once daily for 5 days. Control mice received aerosolized sham solution plus M. pneumoniae, sham solution alone, or FP alone. RESULTS: Mice treated with sham solution or FP alone did not develop airway inflammation or BHR. Mice infected with M. pneumoniae (no FP) developed significant lung inflammation and BHR. FP treatment of infected mice reduced neutrophils in bronchoalveolar lavage fluid (BALF), lung inflammation, and BHR. Expression of Toll-like receptor 2 in lung tissue tended to be down-regulated (P=.18) by FP in infected mice. FP reduced M. pneumoniae by up to 20-fold in lung tissue but not in BALF. CONCLUSION: Inhaled FP suppresses airway inflammation and BHR, which may be caused, in part, by its ability to reduce concentrations of M. pneumoniae in lung tissue.     

白介素17抗体减轻吸烟所致慢性阻塞性肺疾病模型小鼠的气道炎症

目的 研究白介素17(interhukin-17,IL-17)抗体在吸烟所致慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)模型小鼠气道炎症中的作用.方法 C67/BL6雄性小鼠随机分为COPD组(8只)、COPD+IL-17抗体干预组(简称COPD+干预组,8只)和正常对照组(10只).对支气管肺泡灌洗液(BALF)进行细胞计数、染色和分类;用酶联免疫吸附试验检测小鼠肺组织匀浆IL-17水平,观察各组小鼠气道病理改变.结果 COPD组与COPD+干预组相比肺功能差异无统计学意义.COPD组、COPD+干预组小鼠与正常对照组相比BALF细胞总数显著增高[分别为(19.64±1.89)×104/ml,(15.47±2.99)×104/ml和(5.13±1.00)×104/ml,P＜0.01];COPD+干预组较COPD组细胞总数下降(P＜0.01);中性粒细胞比例[分别为(8.58+6.77)%,(22.98±8.46)%]及绝对值[(1.28±0.96)×104/ml,(4.53±1.73)×104/ml]显著下降(P值均＜0.01).肺组织HE染色病理评分COPD+干预组(73.25±18.58)较cOPD组(106.13±36.27)炎症有所减轻(P＜0.05).COPD+干预组小鼠肺组织匀浆中IL-17含量(0.084±0.041)pg/mg pro与COPD组(0.221±0.081)pg/mg pro相比显著降低(P＜0.01).结论 吸烟所致COPD小鼠模型中IL-17参与了中性粒细胞引起的气道炎症,抑制IL-17的表达,可以减少气道内中性粒细胞的数量,减轻气道炎症.     

Elevated levels of antimicrobial peptides in bronchoalveolar lavage fluid in patients with chronic eosinophilic pneumonia

BACKGROUND: Chronic eosinophilic pneumonia (CEP) is an idiopathic pulmonary disease. As the lung is in direct communication with the environment, inhaled antigen may activate immune mechanisms in the airway that may participate in the pathogenesis of idiopathic pulmonary diseases. Defensins are antimicrobial peptides that consist of alpha-defensin (HAD) in neutrophils and beta-defensin (HBD) in epithelial cells. Defensins act as innate immunity against pathogens acquired from the environment and as mediators to induce local inflammation. OBJECTIVES: The aim of the present study was to determine whether immune mechanisms in the airway are induced in CEP patients. METHODS: We measured BALF defensin levels in patients with CEP, acute EP (AEP) and drug-induced eosinophilic pneumonia (drug-EP). We also measured BALF levels of IL-5, GM-CSF, eotaxin and RANTES. These substances can recruit eosinophils. RESULTS: BALF HAD levels were higher in patients with CEP than in those with drug-EP and normal controls. HBD-2 was detected in BALF of 10 of 11 CEP patients and in 3 of 5 AEP patients while its level was below detection in drug-EP patients and normal controls. BALF HBD-2 levels correlated with the proportion of lymphocytes in CEP patients. CONCLUSION: The defensin-linked immune system is activated in CEP but not in drug-EP. This suggests that inhaled antigen(s) may be involved in the pathogenesis of CEP.     

Elevated Tissue Kallikrein Activity in Airway Secretions from Patients with Tracheobronchitis Associated with Prolonged Mechanical Ventilation

The clinical course of patients undergoing prolonged mechanical ventilation is often complicated by the development of purulent tracheobronchitis. The purpose of this study was to assess whether ventilator-associated hypersecretion is associated with elevated levels of tissue kallikrein (TK) activity. TK can induce marked bronchial inflammation in animal models and TK activity is increased in the airway secretions of symptomatic asthmatics. It has not been studied in conditions with predominantly neutrophilic bronchial secretions, although animal data indicate that neutrophil elastase may stimulate TK activity. We measured TK activity in airway secretions of patients undergoing mechanical ventilation for more than 4 weeks (PMV group) and in two comparator groups: patients with cystic fibrosis, who were colonized with Pseudomonas aeruginosa (CF group) and patients undergoing mechanical ventilation for less than one week who did not have clinical evidence of purulent airway secretions (acute mechanical ventilation, AMV group). We also compared the level of neutrophil elastase (NE) activity, an index of neutrophil activation, in the three patient groups. TK and NE activity in the sol phase were measured by the degradation of chromogenic substrates (DL Val-Leu-Arg pNA and N-Methoxy Succinyl Ala-Ala-Pro-Val pNA, respectively). Intergroup differences in cell counts were not significant. However, TK activity was significantly less in the AMV group than in the PMV and cystic fibrosis patients (Kruskal-Wallis ANOVA, p < 0.05). Elastase activity was significantly greater in the CF group (p < 0.05) than in the other two groups. Compared to patients undergoing short-term mechanical ventilation (AMV group), TK activity was elevated in patients with purulent tracheobronchitis associated with prolonged mechanical ventilation (PMV group). The elevation in TK activity in these patients is comparable to levels in sputum from patients with cystic fibrosis (CF group), although the latter had a significantly higher level of NE activity. The observation of increased TK activity in patients with neutrophilic airway inflammation suggests that TK may play a role in modulating inflammation in ventilator-associated tracheobronchitis and may be worthy of further study to determine its source and significance.