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

自然致敏的绵羊吸入蛔虫抗原后，有67%的致敏绵羊同时出现即刻哮喘反应(IAR)和迟发性哮喘反应(LAR)，其余只有IAR。双反应绵羊在激发后8小时对乙酰甲胆碱的气道反应性显著增强，中性粒细胞和嗜酸性粒细胞聚集到呼吸道，而单反应绵羊仅表现出轻微的气道反应性和中性粒细胞募集。预先给予脂质过氧化抑制剂U-74006F和嗜酸性粒细胞趋化活性抑制剂TAK-225可显著降低抗原诱导的哮喘反应，尤其是LAR，并抑制嗜酸性粒细胞重新聚集到双反应绵羊的呼吸道。TAK-225的预处理也可抑制气道高反应性的形成。这些发现表明，脂质过氧化参与了抗原诱导的哮喘反应和嗜酸性粒细胞在呼吸道中的聚集，而聚集的嗜酸性粒细胞参与了LAR和AHR的发展。为了在临床上检验嗜酸性粒细胞的参与，我们分析了36例轻度到重度哮喘患者诱导痰中的炎症细胞和生化物质。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加重而显著升高，且ECP水平与症状积分呈显著正相关，与气流阻塞呈负相关。这些发现提示，哮喘患者的症状和气流障碍与呼吸道嗜酸性粒细胞的激活密切相关。

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.