OXIDATIVE STRESS IN ASTHMA INITIATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 哮喘是一种呼吸道过敏性炎症，影响5%-10%的人口。我们实验室和其他实验室的研究揭示了Th2细胞和细胞因子在诱导这些晚期事件中的关键作用。然而，对于在晚期反应诱导之前并有助于诱导晚期反应的“起始事件”，我们知之甚少。我们之前已经证明，花粉具有NADPH氧化酶活性，在NADPH存在的情况下可以迅速产生超氧化物。在此，我们认为花粉相关的NADPH氧化酶活性在晚期表型的启动中起着关键作用。我们将检验以下假设：-1)花粉NADPH氧化酶增强小鼠的变态反应敏化和抗原诱导的晚期AHR、粘蛋白产生和Th2过敏性炎症。2)RWE的促氧化活性增加了特应性患者即刻ROS的产生和晚期症状以及Th2过敏性炎症。分子机制也将被研究。有过敏性鼻炎症状和豚草皮肤点刺试验阳性的受试者将被招募来研究特定的目标2。在预定的时间点，将收集滤纸和鼻水样本。有晚期症状的患者将被要求参加研究的第二阶段，以确定N-乙酰半胱氨酸(NAC)清除活性氧物种是否可以缓解晚期症状。从这一建议中获得的信息将有助于理解花粉诱导的氧化应激在过敏性疾病发病机制中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is an allergic inflammation of the airways affecting 5-10% of the population. Studies from our lab and others have revealed a critical role of Th2 cells and cytokines in the induction of these late phase events. However, very little is known about the 'initiation events' that precede and contribute to the induction of late phase response. We have previously shown that pollens possess NADPH oxidase activity that can rapidly generate superoxide in the presence of NADPH. Here we propose that pollen-associated NADPH oxidase activity plays a critical role in the initiation of the late phase phenotype.We will test the hypothesis that- 1) pollen NADPH oxidases augment allergic sensitization and antigen-induced late phase AHR, mucin production and Th2 allergic inflammation in mice. 2) pro-oxidant activity of RWE augments immediate ROS production and late phase symptoms and Th2 allergic inflammation in atopic patients. Molecular mechanisms will also be studied. Human subjects with symptoms of allergic rhinitis and a positive ragweed skin prick test will be recruited to study specific aim 2. At predetermined time points filter paper and nasal wash samples will be collected. Patients who have late phase symptoms will be asked to participate in phase II of the study to determine whether scavenging reactive oxygen species by N-acetyl cysteine (NAC) can attenuate the late phase symptoms. Information obtained from this proposal will help understand the role of pollen-induced oxidative stress in the pathogenesis of allergic diseases.