CD86对抗原引起气道嗜酸细胞浸润和气道高反应性作用的研究

目的　探讨ＣＤ８６ 分子对抗原引起气道炎症和气道高反应性的影响,加深认识ＣＤ８６ 在支气管哮喘发病机制中的作用。方法　应用鸡卵清蛋白致敏和刺激ＢＡＬＢ／ｃ 小鼠（ 每组８ 只） 以诱导嗜酸细胞（ＥＯＳ）聚集到气道,收集支气管肺泡灌洗液（ＢＡＬＦ） 细胞并以流式细胞仪检测ＣＤ８６ 分子的表达水平;观察静脉注射抗ＣＤ８６ 单克隆抗体后ＢＡＬＦ中ＥＯＳ数和气道反应性的变化。结果　小鼠经抗原致敏和刺激后ＢＡＬＦ中可以见到大量的ＥＯＳ,气道反应性亦明显升高,ＢＡＬＦ细胞所表达的ＣＤ８６ 水平也随之增高。经抗ＣＤ８６ 单克隆抗体处理后,ＢＡＬＦ中ＥＯＳ数降低了６７％ （ Ｐ＜０－０１）;同时,气道反应性也下降６９％ （ Ｐ＜ ０－０１）。此外,抗ＣＤ８６ 单克隆抗体还可以抑制肺组织局部白细胞介素４ 和白细胞介素５ 的产生。结论　抗ＣＤ８６ 单克隆抗体能够抑制气道ＥＯＳ浸润和降低气道反应性,其作用机制可能是通过抑制局部白细胞介素４ 和白细胞介素５ 产生而实现。提示抑制气道抗原呈递细胞的活性应有益于哮喘的治疗。     

DETECTION OF CIRCULATING ANTIGEN OF CYSTICERCUS CELLULOSAE FORM CYSTICERCOSIS PATIENTS’ SERA WITH INHIBITIVE ELIS

ＤＥＴＥＣＴＩＯＮＯＦＣＩＲＣＵＬＡＴＩＮＧＡＮＴＩＧＥＮＯＦＣＹＳＴＩＣＥＲＣＵＳＣＥＬＬＵＬＯＳＡＥＦＲＯＭＣＹＳＴＩＣＥＲＣＯＳＩＳＰＡＴＩＥＮＴＳ’ＳＥＲＡＷＩＴＨＩＮＨＩＢＩＴＩＶＥＥＬＩＳＡＡＮＤＢＬＯＣＫＩＮＧＩＨＡＺｈａｏＸｕ一Ｄｏｎ...     

STUDIES AND APPLICATION OF PYRCTHROID TREATED BEDNETS FOR CONTROL OF MALARIA VECTORS INP．R．CHINA

ＳＴＵＤＩＥＳＡＮＤＡＰＰＬＩＣＡＴＩＯＮＯＦＰＹＲＣＴＨＲＯＩＤＴＲＥＡＴＥＤＢＥＤＮＥＴＳＦＯＲＣＯＮＴＲＯＬＯＦＭＡＬＡＲＩＡＶＥＣＴＯＲＳＩＮＰ．Ｒ．ＣＨＩＮＡＰａｎＢｏ，ＬｉＺｕ－ｚｉ，ＨｕａｎｇＱｉ－ＬｉｎＩｎｓｔｉｔｕｔｅｏｆＰａｒａｓ...     

吸入血小板活化因子对豚鼠气道反应性影响及机制的研究

将豚鼠暴露于２００ｍｇ／Ｌ的血小板活化因子（ＰＡＦ）气雾，２４小时后测定豚鼠对组胺的气道反应，然后进行支气管肺泡灌洗（ＢＡＬ）。ＰＡＦ处理组的气道反应性显著高于对照组，ＢＡＬ嗜酸性粒细胞（Ｅｏｓ）、低密度Ｅｏｓ（ＨＥｏ）也显著增多。以上表明ＰＡＦ是诱导气道高反应性的重要介质，其作用机制可能与趋化、活化Ｅｏｓ有关。     

NATIONAL PROGRAM OF MALARIA CONTROL OF PEOPLE'S REPUBLIC OF CHINA

ＮＡＴＩＯＮＡＬＰＲＯＧＲＡＭＯＦＭＡＬＡＲＩＡＣＯＮＴＲＯＬＯＦＰＥＯＰＬＥ’ＳＲＥＰＵＢＬＩＣＯＦＣＨＩＮＡＸｕＳｈｕ—ＨｕｉＤｅｐａｒｔｍｅｎｔｏｆｐａｒａｓｉｔｉｃＤｉｓｅａｓｅｓ，ＭｉｎｉｓｔｒｙｏｆＰｕｂｌｉｃＨｅａｌｔｈｏｆＣｈｉｎａ（...     

THE ROLE OF SLEEP IN THE PATHOGENESISOFGASTROESOPHAGEALREFLUX．

ＴＨＥＲＯＬＥＯＦＳＬＥＥＰＩＮＴＨＥＰＡＴＨＯＧＥＮＥＳＩＳＯＦＧＡＳＴＲＯＥＳＯＰＨＡＧＥＡＬＲＥＦＬＵＸ．ＷｉｌｉａｍＣ．Ｏｒｒ，Ｐｈ．Ｄ．ＩＮＴＥＧＲＩＳＢａｐｔｉｓｔＭｅｄｉｃａｌＣｅｎｔｅｒ．ＯｋｌａｈｏｍａＣｉｔｙ，Ｏｋｌａｈｏｍａ，Ｕ...     

间质性肺疾病支气管肺泡灌洗液的酶活性研究

目的探讨支气管肺泡灌洗液（ＢＡＬＦ）多项酶活性与间质性肺疾病（ＩＬＤ）的关系。方法检测３０例ＩＬＤｓ：包括特发性肺纤维化（ＩＰＦ）１８例和结节病（Ｓａｒｃ）１２例与９例正常对照者的ＢＡＬＦ中超氧化歧化酶（ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）、血管紧张素转换酶（ＡＣＥ）和乳酸脱氢酶（ＬＤＨ）活性，并分类计数ＢＡＬＦ细胞成份。结果（１）ＩＰＦ组ＢＡＬＦ中各项酶活性均与对照组间差异有显著性（ＳＯＤ和ＧＳＨ－ＰＸ降低，ＡＣＥ和ＬＤＨ升高）（Ｐ＜０．０５）；而Ｓａｒｃ组仅见ＡＣＥ明显增高（Ｐ＜０．０５）。（２）ＢＡＬＦ－ＡＣＥ与Ｓａｒｃ组淋巴细胞百分比及ＣＤ＋４／ＣＤ＋８比值均有显著线性相关（Ｐ＜０．０５）。结论ＢＡＬＦ中ＳＯＤ、ＧＳＨ－ＰＸ、ＡＣＥ和ＬＤＨ活性测定，有助于进一步探讨ＩＬＤ发病机理和提供辅助诊断依据，ＢＡＬＦ－ＡＣＥ对判断Ｓａｒｃ活动性有重要临床意义。     

嗜酸粒细胞阳离子蛋白在支气管哮喘中的意义

嗜酸粒细胞阳离子蛋白（ＥＣＰ）作为嗜酸粒细胞的特异性活化标志,与迟发性哮喘反应、气道慢性炎症和气道高反应性有着密切的关系,动态检测血清,痰或支气管肺泡灌洗液（ＢＡＬＦ）中的ＥＣＰ水平,可有助于判断气道炎症的存在和程度,预测疾病的发作,同时还可评价抗炎治疗的效果,而痰或ＢＡＬＦ中的ＥＣＰ水平似更能反映气道局部的炎症情况。     

Some recent works on diagnosis and treatment of gastric cancer

ＰＲＥＰＡＲＡＴＩＯＮＡＮＤＵＳＥＳＯＦＭＯＮＯＣＬＯＮＡＬＡＮＴＩＢＯＤＩＥＳＢｙｍｅａｎｓｏｆｃｅｌｆｕｓｉｏｎｔｅｃｈｎｉｃｗｅｅｓｔａｂｌｉｓｈｅｄｓｅｖｅｒａｌｈｙｂｒｉｄｏｍａｃｅｌｌｉｎｅｓｃａｐａｂｌｅｏｆｐｒｏｄｕｃｉｎｇａｎｔ...     

血小板活化因子拮抗剂ONO—6240对抗原引起气道嗜酸性粒细胞浸…

为探讨血小板活化因子选择性拮抗剂ＯＮＯ－６２４０治疗哮喘患的临应用价值，应用鸡卵清蛋白致敏和上鼠复制过敏性哮喘模型，研究ＯＮＯ－６２４０对抗原引起气道嗜酸性粒细胞（ＥＯＳ）浸润的影响。结果表明，正常小鼠支气管肺泡冲洗液中未见到ＥＯＳ；致敏小鼠给予抗原反复吸入刺激后，支气管肺泡冲洗液（ＢＡＬＦ）中ＥＯＳ急剧增多（９．６８×１０＾８／Ｌ±０．７２×１０＾８／Ｌ）。在ＯＮＯ－６２４０治疗各组中，ＯＮＯ     

Interleukin-18 enhances antigen-induced eosinophil recruitment into the mouse airways.

Interleukin-18 (IL-18) has recently been identified as an IFN-gamma-inducing factor. Previous studies have shown that CD4(+) T cells, IL-5, and TNF-alpha mediate, but IFN-gamma and IL-12 (via IFN-gamma production) inhibit antigen-induced eosinophil recruitment into the airways of sensitized mice. Here, we showed that the administration of recombinant murine IL-18 enhanced antigen-induced eosinophil recruitment into the trachea and bronchoalveolar lavage fluids (BALF) of sensitized mice in a dose-dependent manner. The administration of IL-18 enhanced antigen-induced IFN-gamma and TNF-alpha production, but not IL-5 production, in the BALF and lungs of sensitized mice. Neutralizing antibody against TNF-alpha prevented antigen-induced eosinophil recruitment into the BALF of sensitized mice. Although IL-18 enhanced antigen-induced airway eosinophilia, IL-18 did not affect antigen-induced airway hyperresponsiveness in sensitized mice. These results indicate that IL-18, unlike IFN-gamma and IL-12, enhances antigen-induced eosinophil recruitment into the airways in part by increasing antigen-induced TNF-alpha production of sensitized animals. These findings suggest that IL-18 may contribute to the development and exacerbation of airway inflammation in asthma.     

CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea.

In order to determine the role of CD4+ and CD8+ T-cells and of interleukin-5 (IL-5) in causing antigen-induced eosinophil infiltration into the site of airway late-phase reaction, we examined the effect of the in vivo depletion of CD4+ and CD8+ T-cells on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. We also studied the effect of anti-murine IL-5 monoclonal antibody (mAb) on the antigen-induced eosinophil infiltration in the trachea. The eosinophil infiltration into the trachea of ovalbumin (OVA)-sensitized BALB/c mice began to increase 9 h after OVA inhalation and persisted for more than 48 h. The in vivo depletion of CD4+ T-cells by pretreatment with anti-L3T4 mAb significantly decreased the eosinophil infiltration induced by OVA inhalation in the trachea of sensitized mice. However, the in vivo depletion of CD8+ T-cells by pretreatment with anti-Lyt-2 mAb had no significant effect on OVA-induced eosinophil infiltration in the trachea. Pretreatment with anti-murine IL-5 mAb also decreased OVA-induced eosinophil infiltration in the trachea. In contrast, neither disodium cromoglycate nor a selective antagonist for platelet-activating factor CV-6209 decreased OVA-induced airway eosinophilia in the mouse. Our results provide direct evidence that CD4+ but not CD8+ T-cells mediate antigen-induced eosinophil recruitment in the airways and that IL-5 mediates this eosinophil recruitment.     

白细胞介素12重组腺病毒气道内应用对哮喘豚鼠治疗作用的研究

目的　探讨激发前气道内应用白细胞介素 12 (IL 12 )重组腺病毒对过敏性气道高反应的调节作用。方法　以C5 7BL/ 6小鼠经鸡卵蛋白 (OVA)免疫建立哮喘模型 ,实验分 6组 ,每组 6只。激发前气管内单次使用IL 12重组腺病毒 (10 8pfu/mouse) ,观察抗原激发后反应的变化。结果　 (1)小鼠气道内应用IL 12重组腺病毒在肺内可有效表达 ,48h血浆及肺泡灌洗液IL 12分别为 (5 40± 6 0 )U/ml和 (470 0± 80 0 )U/ml,对照病毒和PBS组未检出 ,两组比较差异有显著性 (P <0 0 1)。 (2 )在抗原激发阶段使用IL 12重组腺病毒 ,可明显抑制肺内IL 4[(3 5± 2 0 )ng/ml∶85 0± 2 5 0 )ng/ml]和IL 5[(6 5± 4 5 )ng/ml∶(5 4 0± 14 0 )ng/ml];γ干扰素 (IFN γ)的产生增加 [(6 90 0± 32 0 )ng/ml∶(12 5±3 2 )ng/ml];并明显抑制气道高反应性 [(36 0± 30 )cmH2 O∶(810± 5 0 )cmH2 O];抑制外周血 [(0 7±0 1) %∶(9 2± 0 5 ) % ]及肺泡灌洗液 [(3 5± 0 7)∶(2 1 6± 4 7)× 10 4 /ml]中的嗜酸细胞的水平 ;与对照组比较 (t分别 =7 97、7 92、5 1 6、18 9、9 33、47 1,P均 <0 0 1) ;但与总IgE[(6 5± 9) μg/ml∶(6 7± 10 )μg/ml]及抗原特异性IgE[(32± 8)∶(33± 8)U/ml]比较无明显影响 (P均 >0 0 5 )。     

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.     

Effect of TRFK-5 on airway responsiveness in ovalbumin-treated guinea pigs exposed to tobacco smoke.

Tobacco smoke (TS) exposure can induce airway hyperresponsiveness, especially in asthma. A feature of asthma is eosinophilia. We hypothesized that tobacco smoke exposure enhances eosinophil responsiveness in sensitized guinea pigs. Tobacco smoke-exposed, ovalbumin (OA)-sensitized guinea pigs were treated with TRFK-5 (1.0 mg/kg, intraperitoneal), an anti-interleukin (IL)-5 agent, or its vehicle. Guinea pigs were challenged with aerosols of OA, capsaicin, histamine, and methacholine. TRFK-5 attenuated airway responsiveness to OA but not to capsaicin, histamine, or methacholine. Bronchial alveolar lavage fluid analysis confirmed TRFK-5 attenuated airway eosinophilia in OA-treated guinea pigs. Therefore, airway responsiveness to OA is enhanced by eosinophils or IL-5 itself.     

Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness

Histamine has a variety of airway actions and is considered to be an important mediator in asthma. This study examined the role of endogenous histamine in allergic airway eosinophil recruitment and hyperresponsiveness using L-histidine decarboxylase gene knockout mice. Histamine levels of the airways in L-histidine decarboxylase knockout mice were largely diminished compared with wild-type mice. Inhalation challenge with ovalbumin (OVA) in OVA-sensitized wild-type mice caused eosinophil accumulation in the lung as well as airway hyperresponsiveness to methacholine 3 days after the challenge. The eosinophil recruitment was significantly reduced in the knockout mice. In the bone marrow, the proliferation of eosinophils was enhanced after OVA challenge in the wild-type mice; however, the proliferation was significantly reduced in the knockout mice. The induction of P-selectin in the lung after OVA challenge was also inhibited in the knockout mice. In contrast, airway hyperresponsiveness was not suppressed in the knockout mice. These results suggest that endogenous histamine is involved in the accumulation of eosinophils into the airways after allergic challenge, possibly acting in the bone marrow and producing P-selectin in the airways. Furthermore, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model.     

The effects of intranasal budesonide on allergen-induced production of interleukin-5 and eotaxin,airways, blood,and bone marrow eosinophilia,and eosinophil progenitor expansion in sensitized mice

We have previously demonstrated that allergen inhalation induces expansion of bone marrow eosinophil progenitors in sensitized mice and subjects with asthma and that the inhaled corticosteroid, budesonide, reduced baseline but not allergen-induced increase in bone marrow eosinophil/basophil progenitors (EoB-CFU) in subjects with asthma. Here, we evaluated the effects of intranasal budesonide on allergen-induced increases in interleukin (IL)-5 and eotaxin in the airway and peripheral blood, expansion of bone marrow Eo-CFU and eosinophilia in bone marrow, peripheral blood and airway, as well as airway hyperresponsiveness, in ovalbumin (OVA)-sensitized mice. Budesonide treatment attenuated allergen-induced eosinophilia in bone marrow, peripheral blood, and airways as well as allergen-induced increases in bone marrow eosinophil progenitors but not allergen-induced increases in IL-5 or eotaxin 12 h following the second of two daily exposures to allergen; at later time points treatment was associated with attenuation of IL-5, eosinophilia, Eo-CFU, and airway hyperresponsiveness. These results suggest that a component of the mechanism by which corticosteroid treatment attenuates allergen-induced airway inflammation is through suppression of bone marrow eosinophilopoiesis, and that this is likely not mediated simply through the blocking of IL-5 production at the airway.     

Effect of eotaxin and platelet-activating factor on airway inflammation and hyperresponsiveness in guinea pigs in vivo

Although eotaxin causes selective infiltration of eosinophils into the lung, its role in airway hyperresponsiveness remains unclear. We studied the effects of local administration of eotaxin on airway inflammation and hyperresponsiveness in guinea pigs in vivo. Airway responsiveness to inhaled histamine and differential cell counts in bronchoalveolar lavage fluid (BALF) were evaluated 12 h, 24 h, 3 d, and 7 d after intratracheal instillation of eotaxin. Significant eosinophilia in BALF was observed between 6 h and 7 d after eotaxin administration. Histologically, eosinophil accumulation was observed in the airways but not in the alveoli. In contrast, eotaxin did not affect airway responsiveness between 12 h and 7 d after its administration. We then studied the effects on airway responsiveness of subthreshold doses of interleukin 5, leukotriene D(4) (LTD(4)), and platelet-activating factor (PAF) combined with eotaxin. Neither interleukin 5 nor LTD(4) affected airway responsiveness. After eotaxin treatment, PAF significantly enhanced airway responsiveness without further increases in eosinophil counts. Eotaxin plus PAF significantly increased in eosinophil peroxidase activity in BALF compared with control and with eotaxin alone. These data indicate that eotaxin alone causes eosinophil accumulation in the airways but not hyperresponsiveness, and that additional factors such as PAF are needed to activate eosinophils for the development of airway hyperresponsiveness.     

Both stat5a and stat5b are required for antigen-induced eosinophil and T-cell recruitment into the tissue

Antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by CD4(+) T cells and their cytokines, especially IL-5. In this study, we found that the antigen-induced airway eosinophilia was diminished in Stat5a-deficient (Stat5a(-/-)) mice and Stat5b-deficient (Stat5b(-/-)) mice. We also found that antigen-induced CD4(+) T-cell infiltration and IL-5 production in the airways were diminished in Stat5a(-/- )mice and Stat5b(-/-) mice. Moreover, antigen-induced proliferation of splenocytes was diminished in Stat5a(-/- )mice and Stat5b(-/-) mice, suggesting that the generation of antigen-primed T cells may be compromised in Stat5a(-/-) mice and Stat5b(-/-) mice and this defect may account for the diminished antigen-induced T-cell infiltration into the airways. Interestingly, IL-4 and IL-5 production from anti-CD3-stimulated splenocytes was diminished in Stat5a(-/-) mice and Stat5b(-/-) mice. However, antigen-specific IgE and IgG1 production was diminished in Stat5a(-/-) mice but not in Stat5b(-/-) mice, whereas antigen-specific IgG2a production was increased in Stat5a(-/-) mice, suggesting the enhanced Th1 responses in Stat5a(-/-) mice. Finally, we found that eosinophilopoiesis induced by the administration of recombinant IL-5 was also diminished in Stat5a(-/-) mice and Stat5b(-/-) mice. Together, these results indicate that both Stat5a and Stat5b are essential for induction of antigen-induced eosinophil recruitment into the airways and that the defects in antigen-induced eosinophil recruitment in Stat5a(-/-) mice and Stat5b(-/-) mice result from both impaired IL-5 production in the airways and diminished IL-5 responsiveness of eosinophils. (Blood. 2000;95:1370-1377)     

Inhibition of eosinophilic inflammation in allergen-challenged, IL-1 receptor type 1-deficient mice is associated with reduced eosinophil rolling and adhesion on vascular endothelium

To determine the relative in vivo importance of IL-1 release after allergen challenge to the subsequent endothelial adhesion and recruitment of eosinophils, the authors used ovalbumin sensitization and inhalation challenge to induce airway eosinophilia in IL-1 receptor type 1-deficient and control wild-type mice. Bronchoalveolar lavage (BAL) eosinophil recruitment in IL-1 receptor type 1-deficient mice challenged with ovalbumin (24.3% +/- 6.3% BAL eosinophils) was significantly reduced compared with wild-type mice (63.7% +/- 2.5% BAL eosinophils). To determine whether the inhibition of eosinophil adhesion to vascular endothelium contributed to the inhibition of eosinophil recruitment in IL-1 receptor type 1-deficient mice, the authors used intravital microscopy to visualize the rolling and firm adhesion of fluorescence-labeled mouse eosinophils in the microvasculature of the allergen-challenged mouse mesentery. Eosinophil rolling, eosinophil firm adhesion to endothelium, and transmigration across endothelium (peritoneal eosinophils) were significantly inhibited in allergen-challenged IL-1 receptor type 1-deficient mice compared with wild-type mice. Overall, these studies demonstrate that cytokines such as IL-1, released after allergen challenge, are important in the induction of endothelial cell adhesiveness, a prerequisite for the recruitment of circulating eosinophils. (Blood. 2000;95:263-269)