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THE ROLE OF NEUTROPHIL AND EOSINOPHIL IN BRONCHIAL ASTHMA.

中性粒细胞和嗜酸性粒细胞在支气管哮喘中的作用。

基本信息

批准号：
05670523
负责人：
FUJIMOTO Keisaku
金额：
$ 1.54万
依托单位：
SHINSHU UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670523/
关键词：
Bronchial asthma neutrophil Eosinophil Late asthmatic response Airway hyperreactivity Neutrophil elastase Leukotriene B_4 Ascaris-sensitized sheep 緬羊アスカリス Leukotriene B_4 Thromboxane B_2 PAF 気道過敏性炎症細胞

项目摘要

In this project two studies were performed. First study was to see the effect of specific neutrophil elastase inhibitors, ONO-5046 and FRl34043, on antigen-induced asthmatic responses in allergic dual responded sheep. Ascaris suum inhalation over 20 min induced early (IAR) and late (LAR) bronchoconstriction, airway hyperreactivity to methacholine (AHR), increases in recovered neutrophils and eosinophils and the concentrations of leukotriene B_4 (LTB_4) and thromboxane B_2 (TXB_2) in bronchoalveolar lavage fluid (BALF) during LAR.Continuous infusion of ONO-5046 before antigen challenge signficantly reduced both early and late bronchoconstriction. The inhibitory effect was marked in late bronchoconstriction. Also, the drug significantly reduced the antigen-induced AHR,neutrophil accumulation in the airway and increase in LTB_4 during LAR.Another neutrophil elastase inhibitor, FR134043, also reduced both IAR and LAR.These findings suggest that neutrophil elastase is involved in antigen-induced bronchoconstriction and AHR mediated by neutrophil accumulation and 5-lipoxygenase products in allergic sheep. Second study was to see the effects of specific LTB_4 receptor antagonist, ONO-4057, on asthmatic responses in the same allergic sheep model. The oral administration of the drug before antigen challenge significantly reduced the late phase bronchoconstriction along with the inhibition of eosinophil accumulation in the airway. Also, the drug treatment significantly reduced AHR 8h after antigen challenge. These finding suggest that LTB_4 is an important chemotactic factor for eosinophils and the accumulated eosinophil Plays an important role in the development of LAR and AHR.

在该项目中，进行了两项研究。第一项研究是观察特异性中性粒细胞弹性蛋白酶抑制剂ONO-5046和FR 134043对过敏性双重应答绵羊中抗原诱导的哮喘应答的影响。吸入猪蛔虫20分钟以上可诱导早期（IAR）和晚期（LAR）支气管收缩，气道对乙酰甲胆碱（AHR）的高反应性，BALF中白三烯B_4（LTB_4）和血栓素B_2（TXB_2）浓度升高5046在抗原攻击前显著降低早期和晚期支气管收缩。在晚期支气管收缩中抑制作用显著。另一种中性粒细胞弹性蛋白酶抑制剂FR 134043也能明显降低抗原诱导的支气管收缩反应和由中性粒细胞聚集和5-脂氧合酶产物介导的AHR。第二项研究是观察LTB_4受体拮抗剂ONO-4057对过敏性绵羊哮喘反应的影响。抗原激发前口服药物可显著降低晚期支气管收缩沿着抑制气道中嗜酸性粒细胞蓄积。此外，药物治疗显著降低抗原攻击后8h的AHR。提示LTB_4是嗜酸性粒细胞的重要趋化因子，嗜酸性粒细胞的聚集在LAR和AHR的发生发展中起重要作用。