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

吸入蛔虫抗原刺激自然致敏的羊，约67%的致敏羊均可引起立即哮喘反应（IAR）和晚期哮喘反应（LAR），而其余羊仅表现为IAR。在刺激8小时后，双应答羊的气道对乙酰胆碱的反应性和中性粒细胞和嗜酸性粒细胞的招募也显著增加，而单应答羊的气道反应性和中性粒细胞的招募则略有增加。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预处理显著降低了双应答羊的抗原诱导的哮喘反应，尤其是LAR，并抑制了嗜酸性粒细胞向气道的募集。TAK-225预处理还能抑制气道高反应性（AHR）的发展。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向气道的募集，而嗜酸性粒细胞的积累促进了LAR和AHR的发展。为了探讨嗜酸性粒细胞在临床中的作用，我们分析了36例轻至重度哮喘患者诱导痰中的炎症细胞群和生化物质。随着哮喘严重程度的增加，患儿嗜酸性粒细胞数量和嗜酸性阳离子蛋白（ECP）水平均显著升高，且ECP水平与症状评分呈显著正相关，与气流阻塞呈显著负相关。这些发现提示，气道内嗜酸性粒细胞的激活与哮喘的症状和气流阻塞密切相关。

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.