OXIDATIVE STRESS IN ASTHMA INITIATION

点击翻译按钮获取中文摘要

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.