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THE ROLE OF INFLAMMATORY CELLS IN ANTIGENINDUCED ASTHMATIC RESPONSES AND AIRWAY HYPERRESPONSIVENESS.

炎症细胞在抗原诱导的哮喘反应和气道高反应性中的作用。

基本信息

批准号：
07670663
负责人：
HONDA Takayuki
金额：
$ 1.34万
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 Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670663/
关键词：
Bronchial asthma Antigen-induced asthmatic response Eosinophil Lipid peroxidation Ascaris-sensitized sheep Airway hyperreactivity Induced sputum Eosinophil cationic protein 緬羊即時型喘息反応遅発型喘息反応 ECP 遅発型の喘息反応 U74006F TAK-225

项目摘要

The inhaled provocation of Ascaris antigen to naturally sensitized sheep induced both immediate asthmatic response (IAR) and late asthmatic response (LAR) in about 67% of all sensitized sheep, however, the rest showed only IAR.The dual respondent sheep also showed an significant increased airway reactivity to methacholine and recruitment of neutrophils and eosinophils into the airway 8 hour after the provocation, whereas the single respondent sheep showed a slight increase in airway reactivity and neutrophils recruitment alone. The pretreatment with the inhibitor of lipid peroxidation, U-74006F,and the inhibitor of eosinophil chemotactic activity, TAK-225, significantly reduced antigen-induced asthmatic responses, especially LAR together with the inhibition of eosinophil recruitment into the airway in dual respondent sheep. The pretreatment of TAK-225 also inhibited the development to airway hyperreactivity (AHR). These findings suggest that lipid peroxidation is involved in antigen-induced asthmatic responses and eosinophil recruitment into the airway, and that the accumulated eosinophils contribute to the development of LAR and AHR.In order to examine the involvement of eosinophils clinically, we analyzed the inflammatory cell populations and biochemical substances in induced sputum from mild to severe asthmatics (n=36). The eosinophil numbers and eosinophil cationic protein (ECP) levels were significantly increased in accordance with the severity of asthma, and the ECP levels were significantly positively correlated with the symptom score and negatively correlated with the airflow obstruction. These findings suggest that the eosinophil activation in the airway is closely linked to the symptoms and airflow obstruction of asthma.

吸入蛔虫抗原激发自然致敏绵羊后，约67%的致敏绵羊同时出现即刻哮喘反应（IAR）和迟发哮喘反应（LAR），其余绵羊仅出现IAR。激发后8h，气道对乙酰甲胆碱的反应性显著增加，中性粒细胞和嗜酸性粒细胞聚集到气道，而单个应答羊仅显示气道反应性和中性粒细胞募集的轻微增加。脂质过氧化抑制剂U-74006 F和嗜酸性粒细胞趋化活性抑制剂TAK-225预处理可显著降低抗原诱导的哮喘反应，尤其是LAR以及抑制嗜酸性粒细胞募集至双重应答绵羊气道。TAK-225预处理还可抑制气道高反应性（AHR）的发展。这些结果表明，脂质过氧化参与了抗原诱导的哮喘反应和嗜酸性粒细胞向气道的募集，而嗜酸性粒细胞的积累有助于LAR和AHR的发展。为了研究嗜酸性粒细胞的参与临床，我们分析了轻至重度哮喘患者（n=36）诱导痰中的炎症细胞群和生化物质。嗜酸性粒细胞数和嗜酸性粒细胞阳离子蛋白（ECP）水平随哮喘严重程度的增加而显著升高，且ECP水平与症状积分呈显著正相关，与气流阻塞呈显著负相关。提示气道嗜酸性粒细胞的活化与哮喘的症状和气流阻塞密切相关。