超表达Serrate1树突细胞对支气管哮喘小鼠CD4+CD25+T细胞分化的作用

2组小鼠肺组织的病理学改变.结果 与对照组相比,Serrate1组可使哮喘小鼠脾脏CD4+CD25+T细胞数量明显增多,占CD4+T细胞的百分数亦明显增高;Serrate1组CDZT细胞IL-10、CTLA-4、TGFβ1 mRNA表达明显增强,且气道炎症明显减轻.结论 超表达Serrate1 DC能抑制哮喘小鼠CD4+T细胞分化和促进CD4+T细胞分泌抑制性细胞因子,有效改善哮喘小鼠气道炎症,表明DC可通过Notchl/Serrate 1信号通路影响调节性T细胞分化、逆转哮喘免疫耐受缺陷.     

地塞米松对哮喘小鼠CD4+CD25+调节性T细胞及IL-4、IL-10水平的影响

目的 探讨地塞米松对哮喘小鼠CD4+ CD25+调节性T细胞及IL-4、IL-10水平的影响.方法 30只雄性BALB/c小鼠随机分为三组:正常对照组、哮喘组和地塞米松组.利用卵清白蛋白腹腔注射和雾化吸入制备哮喘模型;通过流式细胞仪检测各组小鼠脾脏单个核细胞CD4+ CD25+调节性T细胞占CD4+T细胞的百分比;使用免疫组织化学方法分析各组IL-4在小鼠肺组织中的表达情况;用酶联免疫吸附试验检测各组小鼠血清IL-10的水平.结果 哮喘组脾脏单个核细胞CD4+CD25+调节性T细胞百分比及IL-10的表达水平较正常对照组和地塞米松组降低(P＜0.05),哮喘组IL-4水平较正常对照组和地塞米松组增高(P＜0.05).结论 地塞米松的抗炎作用可能通过上调CD4+ CD25+调节性T细胞、调节性T细胞亚群失衡的途径来实现.     

CD4~+ CD25~+调节性T细胞在血吸虫可溶性虫卵抗原影响哮喘中的作用研究

目的研究血吸虫可溶性虫卵抗原(SEA)与哮喘发生的关系及其对CD4+CD25+调节性T细胞(CD4+CD25+Treg)及相关基因Foxp3表达的影响。方法 BALB/C小鼠腹腔及足垫共注射SEA 50μg/只,每周1次,共4次。对照组注射生理盐水。然后用卵清白蛋白(OVA)诱导小鼠产生过敏性哮喘。剖杀小鼠,取肺组织,做病理学检查;收集支气管肺泡灌洗液(BALF),涂片、染色后进行细胞分类计数;分离脾细胞,用流式细胞仪检测CD4+CD25+调节性T细胞(CD4+CD25+Treg)占CD4+T细胞的比例;提取脾脏RNA,以逆转录得到的cDNA为模板扩增Foxp3基因,检测脾脏Foxp3mRNA表达水平。结果 SEA免疫并OVA致哮喘组小鼠肺组织炎症较OVA单纯哮喘对照组轻,只有少量炎性细胞浸润。BALF涂片染色检查SEA免疫组BALF中的细胞密度低于对照组,其中嗜酸粒细胞占总细胞数的(2.22±1.52)%,对照组占(19.93±4.08)%,差异有统计学意义(P<0.05);流式细胞仪检测SEA免疫组小鼠脾细胞中CD4+CD25+Treg占CD4+T细胞总数的(32.24±2.19)%,对照组占(27.41...     

间充质干细胞移植对小鼠CD4CD25调节性T细胞表达的影响

目的探讨间充质干细胞(MSC)移植对载脂蛋白E基因敲除(apoE-/-)小鼠CD4CD25调节性T细胞表达的影响。方法分离培养apoE-/-小鼠骨髓MSC并进行鉴定。将30只apoE-/-小鼠分为阴性对照组(Neg组)、阳性对照组(Pos组)和MSC移植组(MSC组),每组10只,Pos组和MSC组分别从尾静脉注射DMEM和MSC。比较各组小鼠不同组织中CD4CD25调节性T细胞的数目和功能;利用ELISA法检测各组小鼠脾细胞炎性因子浓度。结果与Neg组和Pos组比较,MSC组脾细胞中CD4CD25/CD4细胞数目显著增加,Foxp3CD25T细胞显著增加,CD4CD25调节性T细胞增殖反应下降;上清液中转化生长因子β和白细胞介素10浓度显著升高,干扰素γ浓度显著下降,差异有统计学意义(P<0.05);Neg组与Pos组比较,差异无统计学意义(P>0.05)。结论 MSC移植能上调apoE-/-小鼠CD4CD25调节性T细胞数目并增强其功能,抑制动脉硬化炎性反应和抗动脉硬化作用。     

骨髓间充质干细胞逆转支气管哮喘小鼠气道重构及其机制

目的探讨骨髓间充质干细胞(BMSCs)逆转支气管哮喘小鼠气道重构的作用及机制。方法构建卵清蛋白致敏/激发肺部变应性炎症小鼠模型,实验分为哮喘组、治疗组和空白对照组。哮喘组和治疗组分别在1 d、8 d使用鸡卵清蛋白(OVA)腹腔注射致敏,第15、16、17天使用OVA气道内滴入激发哮喘。治疗组在第14天激发后腹腔注射2 ml含1×10~7个BMSCs的培养液。空白对照组全部采用等量磷酸盐缓冲液(PBS)处理。末次激发后48 h处死小鼠,留取血清进行白细胞介素(IL)-4及干扰素(IFN)-γ的检测,留取外周血进行Treg检测、留取肺脏进行病理检测、留取肺泡灌洗液进行细胞种类和数量的检测。结果哮喘组和治疗组模型构建成功,HE染色显示小鼠肺脏均出现明显病理变化,如肺组织有明显炎症细胞浸润,同时有血管壁水肿及上皮细胞坏死的情况。而对照组未见任何病理损伤。酶联免疫吸附试验(ELISA)检测结果显示哮喘组和治疗组血清IL-4的含量较对照组明显增高,哮喘组增高更明显,差异有统计学意义(P0. 05),同时血清IFN-γ的含量较对照组明显降低,哮喘组降低更明显,差异有统计学意义(P0. 05)。检测三组外周血中Treg细胞含量的变化显示,与对照组相比,哮喘组和治疗组Treg明显降低,哮喘组降低显著,差异有统计学意义(P0. 05)。检测各组肺泡灌洗液结果显示,哮喘组和治疗组肺部嗜酸性粒细胞(EOS)、中性粒细胞、淋巴细胞等炎症细胞数量显著增加,与对照组相比差异有统计学意义(P0. 05)。结论 BMSCs移植后可以有效迁移到肺损伤部位,同时通过调节免疫微环境可以达到逆转支气管哮喘小鼠气道重构的目的,其机制可能与CD4~+CD25~+Treg及Th1/Th2的比例调节等有关。     

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.     

小鼠骨髓间充质干细胞SCA-1~+/CD45~+/CD31~+亚群抗凋亡能力的研究

目的:探讨小鼠骨髓间充质干细胞(mBMSCs)各亚群在心肌修复中抗凋亡能力。方法:以小鼠心肌干细胞表面分化抗原检测mBMSCs后以CD45、CD31为标准分选得到小鼠骨髓间充质干细胞4个亚群。体外将4个亚群采用无血清低氧(5%)培养,流式细胞仪检测各组的凋亡率。分别将细胞注入小鼠心梗模型体内,注射后48h完成心功能测定。结果:SCA-1+/CD45+/CD31+组抗凋亡能力最强,心脏彩超提示心功能恢复亦优于其他各组。结论:小鼠骨髓间充质干细胞SCA-1+/CD45+/CD31+组抗凋亡能力明显优于其他组,治疗后心功能恢复亦优于其他各组。     

外源性间充质干细胞减轻支气管哮喘小鼠气道炎症的研究

目的 观察鸡卵清蛋白诱导小鼠支气管哮喘(简称哮喘)模型中外源性间充质干细胞(mesenchymal stem cells,MSC)在哮喘小鼠肺组织气道炎症中的作用.方法 45只雌性SPF级C57BL/6小鼠,体质量18～22 g.随机分为对照组(P:P:P)、哮喘组(O:P:O)和MSC治疗组(O:M:O).哮喘组与MSC治疗组第1天和第8天致敏,第15天、第16天和第17天使用OVA气道内滴入激发哮喘.MSC治疗组于哮喘造模第14天移植外源性MSC.对照组小鼠予PBS处理.三组小鼠于末次激发结束后24 h(第18天)处死,取支气管肺泡灌洗液上清,ELISA检测IL-5、IL-9及β-氨基己糖苷酶;支气管肺泡灌洗液细胞计数总细胞数、嗜酸粒细胞数;取肺组织行病理切片苏木精-伊红染色观察肺部气道炎症情况.结果 ①MSC下调了哮喘小鼠气道局部炎症;②MSC减轻了哮喘小鼠肺组织中的炎细胞浸润;③MSC减轻了哮喘小鼠气道中的肥大细胞脱颗粒现象;④MSC抑制了哮喘小鼠过度的Th2变态反应.结论 外源性MSC通过抑制Th2变态反应,减轻哮喘肺组织的气道炎症.     

外源性间充质干细胞减轻支气管哮喘小鼠气道炎症的研究

目的观察鸡卵清蛋白诱导小鼠支气管哮喘（简称哮喘）模型中外源性间充质干细胞（mesenehymal stem cells,MSC）在哮喘小鼠肺组织气道炎症中的作用。方法45只雌性SPF级C57BL／6小鼠,体质量18-22g。随机分为对照组（P：P：P）、哮喘组（O：P：O）和MSC治疗组（O：M：O）。哮喘组与MSC治疗组第1天和第8天致敏,第15天、第16天和第17天使用OVA气道内滴入激发哮喘。MSC治疗组于哮喘造模第14天移植外源性MSC。对照组小鼠予PBS处理。三组小鼠于末次激发结束后24h（第18天）处死,取支气管肺泡灌洗液上清,ELISA检测IL-5、IL-9及β-氨基己糖苷酶;支气管肺泡灌洗液细胞计数总细胞数、嗜酸粒细胞数;取肺组织行病理切片苏木精-伊红染色观察肺部气道炎症情况。结果①MSC下调了哮喘小鼠气道局部炎症;②MSC减轻了哮喘小鼠肺组织中的炎细胞浸润;③MSC减轻了哮喘小鼠气道中的肥大细胞脱颗粒现象;④MSC抑制了哮喘小鼠过度的Th2变态反应。结论外源性MSC通过抑制Th2变态反应,减轻哮喘肺组织的气道炎症。     

雷公藤甲素通过IL-10/Th17细胞调节哮喘小鼠气道炎症

目的:探索雷公藤甲素对哮喘小鼠外周血白细胞介素-10(IL-10)、辅助性T17(Th17)细胞及气道炎症的影响。方法:32只雌性BALB/c小鼠随机分为对照组、哮喘组、雷公藤甲素组、地塞米松组,每组8只。对照组给予生理盐水致敏与激发,哮喘组给予卵清蛋白(OVA)致敏及激发,雷公藤甲素组在每次激发前给予40μg/(kg·d)雷公藤甲素腹腔注射干预,地塞米松组在每次激发前给予1 mg/(kg·d)地塞米松腹腔注射干预。最后一次激发24 h后收集各组小鼠肺泡灌洗液进行细胞分类计数,检测外周血细胞因子IL-10、外周血CD4+淋巴细胞中Th17细胞比例,对肺组织进行HE染色,评估小鼠气道炎症的变化。结果:哮喘组小鼠IL-10浓度明显低于对照组,Th17细胞比例明显高于对照组,且肺泡灌洗液细胞总数、嗜酸性粒细胞计数、中性粒细胞计数、气道周围炎症评分均明显高于对照组(均P 0. 01)。雷公藤甲素组及地塞米松组IL-10浓度较哮喘组明显升高,Th17细胞比例较哮喘组明显下降,且肺泡灌洗液细胞总数、嗜酸性粒细胞计数、中性粒细胞计数、气道周围炎症评分明显低于哮喘组(均P 0. 05),而雷公藤甲素组及地塞米松组之间上述指标比较差异无统计学意义(均P 0. 05)。结论:雷公藤甲素可能通过IL-10对Th17细胞的调节作用减轻气道周围炎症,为哮喘的临床治疗提供新的靶点。     

地塞米松对哮喘大鼠气道重建、肥大细胞及IL-10的影响

目的观察地塞米松对哮喘大鼠模型气道重建和肺组织肥大细胞、IL-10的影响,探讨地塞米松在气道炎症和气道重塑中的作用机制,为临床治疗提供依据。方法采用卵白蛋白（OVA）腹腔注射致敏和雾化吸入激发建立哮喘大鼠模型,30只SD大鼠随机分为3组,正常对照组（A）、哮喘组（B）、地塞米松干预组（C）,每组10只。对肺组织切片行苏木精-伊红（HE）染色观察气道重塑情况。采用免疫组化和图像分析技术测定各组大鼠肺组织肥大细胞、IL-10的表达。结果哮喘组动物出现管壁增厚、平滑肌增生、黏液分泌增加等气道重塑的特征性改变,免疫组化染色显示气道各层细胞及炎性细胞均有IL-10表达减少。地塞米松干预组与哮喘组比较,炎症反应轻微,平滑肌增生、黏液分泌不明显,免疫组化染色显示各类细胞IL-10表达增高,与对照组比较差异有统计学意义。结论长期吸入变应原可导致气道重塑,肥大细胞、IL-10在气道重塑中发挥重要作用,地塞米松可通过抑制肥大细胞脱颗粒、增加IL-10表达发挥抑制炎症作用,进而缓解哮喘大鼠气道重塑的发生。     

CD+4CD+25 T淋巴细胞对支气管哮喘小鼠气道炎症的影响及作用机制

目的探讨CD+4 CD+25 T淋巴细胞(Treg细胞)对支气管哮喘(简称哮喘)小鼠气道炎症的影响及作用机制.方法 60只小鼠按随机数字表法分为3组,每组20只.哮喘组(A组)小鼠于第1、13天以鸡卵白蛋白(OVA)0.1 ml腹腔注射致敏,第21～29天雾化吸入2% OVA生理盐水溶液10 ml激发 30 min后建立小鼠哮喘模型.生理盐水对照组(B组)以生理盐水10 ml替代OVA处理.去除T淋巴细胞哮喘组(C组)去除小鼠体内CD+25 T淋巴细胞后再按A组方法复制小鼠哮喘模型(用药剂量和方法同A组).分离A、B、C 3组小鼠脾脏淋巴细胞,用流式细胞仪(FACS)检测Treg细胞数量,计算其占CD+4 T淋巴细胞的百分比;分离CD+4 T淋巴细胞,用逆转录-聚合酶链反应(RT-PCR)法检测白细胞介素10(IL-10)、转化生长因子β1(TGF-β1)和细胞毒性T淋巴细胞抗原4 mRNA(CTLA-4 mRNA)的表达;同时对肺组织行苏木精-伊红 (HE)染色,观察小鼠肺组织的炎症改变. 结果经过OVA反复激发,A组小鼠脾脏Treg细胞占CD+4 T淋巴细胞的百分比为(3.10±0.03)%,B组为(9.60±0.04)%,A、B两组间及C组分别与A、B组比较差异均有统计学意义(P均<0.01); IL-10、TGF-β1和CTLA-4 mRNA的表达A组分别为0.250±0.040、0.29±0.03、0.28±0.06, B组分别为0.480±0.080、0.47±0.05、0.50±0.03、C组分别为0.080±0.020、0.11±0.04、0.12±0.05,A、B两组及C组分别与A、B组比较差异均有统计学意义(P均<0.01).与B组比较,A组肺部以嗜酸粒细胞浸润为主要表现的炎症改变明显增强,C组则较A、B组显著增强.结论 Treg细胞的数量减少和(或)功能障碍可能是哮喘气道炎症发生发展的重要机制.     

T cells in sputum of asthmatic patients are activated independently of disease severity or control

BackgroundT cells play an important role in bronchial asthma. Although airway CD4+ T cells have been extensively studied previously, there are hardly any studies relating CD8+ T cell activation and disease symptoms.ObjectivesThe aim of this study was to analyse the association between T cell activation in induced sputum T cells and asthma severity and control; and to evaluate T cell subpopulations in the same subgroups.MethodsFifty allergic asthmatic patients were recruited and lung function testing was performed. Airway cells were obtained by sputum induction via inhalation of hypertonic saline solution. CD3, CD4, CD8, CD28, CD25 and CD69 were studied by flow cytometry in whole induced sputum and peripheral blood cells.ResultsTotal induced sputum T cells and CD8+ T cells had a higher relative percentage of the activation markers CD25 and CD69 in comparison with peripheral blood. In sputum, the relative percentage of CD25 was higher in CD4+ T cells when compared to CD8+ T cells and the reverse was true regarding CD69. However, neither disease severity nor control were associated with the relative percentage of CD25 or CD69 expression on T cells in sputum.ConclusionsBoth CD4+ and CD8+ T cells are activated in the lungs and peripheral blood of asthmatic patients. However, with the possible exception of CD69+ CD8+ T lymphocytes in the sputum, there is no association between T cell activation phenotype in the target organ and disease severity or control.     

钙调神经磷酸酶在支气管哮喘大鼠气道重塑中的作用

目的 通过测定支气管哮喘(简称哮喘)大鼠肺组织中钙调神经磷酸酶(calcineurin,CaN)蛋白、Mrna的表达及CaN的活性,探讨CaN在哮喘大鼠气道重塑中的作用.方法 将20只Wistar大鼠随机分为哮喘组和对照组,每组10只.鸡卵清白蛋白溶液致敏及激发复制大鼠哮喘模型.HE染色观察气道炎症情况;图像分析观察支气管管壁厚度;实时定量(Real-time)PCR测定肺组织中CaN Mrna水平;免疫组织化学法检测肺组织中CaN蛋白的相对表达量;生物化学法检测大鼠肺组织CaN活性;流式细胞仪测定外周血单个核细胞细胞周期时相分布;ELISA法测定血浆中白介素4(IL-4)和肿瘤坏死因子α(TNF-α)的含量.结果 ①哮喘组大鼠支气管管壁厚度较对照组明显增加(P＜0.01);②哮喘组大鼠肺组织中CaNmRNA水平的相对表达量、CaN蛋白的相对表达量及CaN的活性均较对照组高(分别P＜0.05、P＜0.01和P＜0.01);③哮喘组大鼠血浆中IL-4和TNF-α含量较对照组明显增加(分别P＜0.01,P＜0.05);④与对照组相比,哮喘组大鼠外周血单个核细胞处于G0/G1期的百分率降低,处于S期、S+G2/M期百分率增加(P值均＜0.01);⑤大鼠肺组织CaN活性分别与大鼠支气管管壁厚度呈正相关(P＜0.01),与处于S期、S+G2/M期的外周血单个核细胞百分率呈正相关(P值均＜0.05),与血浆中IL-4的含量呈正相关(P＜0.05);血浆中IL-4含量与TNF-α含量及大鼠支气管管壁厚度亦呈正相关(P值均＜0.05).结论 哮喘大鼠肺组织CaN的活性增加,其可能通过促进外周血单个核细胞的分裂、增殖及活化产生IL-4和TNF-α而参与哮喘气道重塑的形成.     

热休克因子1在支气管哮喘中的表达

目的观察支气管哮喘（简称哮喘）小鼠肺组织中热休克因子1（heatshockfactor-1,HSF-1）的表达及其在哮喘中的作用。方法32只SPF级BALB／c小鼠随机分为正常对照组（N组）、急性哮喘组I（A组）、急性哮喘组Ⅱ（B组）、慢性哮喘组（C组）4组,每组8只。用10％鸡卵白蛋白（ovalbumin,OVA）致敏和1％OVA激发小鼠建立哮喘模型。HE染色鉴定模型;免疫组织化学、Western-blot法分析各组小鼠肺组织中HSF-I的表达和定位情况。结果支气管肺泡灌洗液（bronchoalvcolarlavagefluid,BALF）分析提示哮喘组嗜酸粒细胞绝对计数及分类计数较N组皆有显著增高（Pd0．05）;HE染色提示哮喘组与N组相比出现嗜酸粒细胞浸润增多、纤毛脱失、黏液栓形成等改变;免疫组织化学结果显示HSF-1在哮喘模型各组小鼠表达呈阳性结果,主要定位在支气管上皮细胞、部分肺泡上皮细胞和炎症细胞中,B组表达阳性信号最强,而在N组中表达较弱;Westernblot检测发现HSF-1在哮喘模型组表达量较对照组为高,灰度值通过单因素方差分析,差异具有统计学意义（P〈0．05）,其中B组的表达量较A组高,差异具有统计学意义（Pd0．05）。结论HSF-1在哮喘小鼠肺组织中主要表达于小鼠的支气管上皮细胞,部分肺泡上皮细胞和炎症细胞;HSF-1在哮喘中表达增高,且表达量与炎症的严重程度相关。     

Effects and Mechanism of Arsenic Trioxide on Reversing the Asthma Pathologies Including Th17-IL-17 Axis in a Mouse Model

In traditional Chinese medicine, arsenous compounds, including arsenic trioxide (ATO), are often used to treat many diseases, which are safe and effective. Recently, studies have indicated that Th17- IL-17 involved in the pathogenesis and development of asthma. The goal of this study was to investigate the effect and mechanism of ATO on asthma, especially the Th17- IL-17 axis.We used oval bumin (OVA)-immunized mice as a model for asthma and treated mice with ATO or dexamethasone. The mice were then monitored airway responsiveness, airway inflammation, mucus production, IL-17 levels in BALF and the positive rate of Th17 cells. In vitro, CD4+ T cells from splenic cell suspensions were separated and purified. We measured the expression of IL-17 and caspase-12 protein in purified CD4+ T cells, and detected IL-17 levels in CD4+ T lymphocyte culture solution with or without ATO. Moreover, apoptosis, mitochondrial membrane potential, cytosolic calcium were analyzed. We found that ATO could reduce airway responsiveness, airway inflammation, mucus hyperplasia, the expression of IL-17 in BALF and the positive rate of Th17 cells at a level comparable to treatment with DXM. In vitro data suggested that ATO can induce CD4+ T cells apoptosis, cause mitochondrial dysfunction, Ca2+ overload and promote caspase-12 activation. Our study suggested that ATO had potential medical value for the treatment of human asthma..     

Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling

It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly.     

Airway inflammation is present during clinical remission of atopic asthma.

Symptoms of atopic asthma often disappear at puberty. However, asthmatic subjects in clinical remission will frequently have a relapse later in life. The aim of this study was to investigate whether subjects in clinical remission of atopic asthma have persistent airway inflammation and/or airway remodeling. Bronchial biopsies were obtained from subjects in clinical remission, asthmatic subjects, and healthy control subjects. The presence and/or activation state of eosinophils, mast cells, macrophages, T lymphocytes, interleukin (IL)-5, eotaxin, and inducible nitric oxide synthase (iNOS) were analyzed. Results were compared with less invasive indicators of airway inflammation. Also aspects of airway remodeling were determined. Eosinophils, T cells, mast cells, and IL-5 were significantly elevated in the airway mucosa of subjects in remission compared with control subjects. Also, blood eosinophil cell counts were significantly higher in subjects in clinical remission. Blood eosinophil cell counts, exhaled nitric oxide (eNO) levels, and bronchial response to adenosine-5'-monophosphate correlated significantly with the quantity of tissue eosinophils. Significant airway remodeling was found in subjects in clinical remission. Our study has shown ongoing airway inflammation and airway remodeling in adolescents in clinical remission of atopic asthma. Subclinical airway inflammation may well determine the risk of an asthma relapse later in life.