AFFERENT NERVE ACTIV IN ISOL TRACHEA OF INF MONKEYS EXP TO OZONE & ALLERGEN

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目的：在灵长类动物和人类中，肺发育的很大一部分发生在出生后，包括发育中的呼吸道的增殖和神经支配。我们记录了在出生后发育期间暴露于臭氧（O3）加过敏原（HDMA）的6个月大的猴子的呼吸道上皮内神经明显少于在过滤空气（FA）中长大的动物。此外，神经在上皮中的分布也发生了改变。为了确定吸入皮质类固醇是否可以逆转这些变化，将1个月大的恒河猴致敏，然后暴露于FA或O3 （0.5 PPM， 6小时/天，5天，每隔一周）加HDMA（2小时/天，3天，每隔一周）5个月。一半的FA和O3/HDMA动物从3-6个月开始每天吸入布地奈德（BUD） （0.33 mg/5分钟）。采用免疫反应蛋白基因产物（PGP） 9.5对肺内气道上皮内神经的密度和分布进行免疫组织化学评价。除了O3/HDMA猴气道上皮内神经明显少于FA猴外，O3/HDMA猴气道中含有异常PGP 9.5免疫反应细胞簇。BUD治疗不能促进上皮粘膜的再神经支配。此外，PGP 9.5阳性纤毛细胞显著增加。

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. Objective: In primates and humans, a substantial portion of lung development occurs postnatally, including proliferation and innervation of the developing respiratory tract. We documented that the airways of 6 month-old monkeys exposed to ozone (O3) plus allergen (HDMA) during postnatal development had significantly fewer intraepithelial nerves than animals raised in filtered air (FA). In addition, the nerves had an altered distribution in the epithelium. To determine whether inhaled corticosteroids could reverse these changes, 1-month-old rhesus monkeys were sensitized and then exposed for 5 months to FA or O3 (0.5 PPM, 6hr/day, 5days, every other wk) plus HDMA (2 hr/day, 3 days, every other wk). One half of the FA and O3/HDMA animals were given inhaled budesonide (BUD) (0.33 mg/5 minutes) daily from 3-6 months.The density and distribution of intraepithelial nerves in intrapulmonary airways was evaluated immunohistochemically using immunoreactivity for protein gene product (PGP) 9.5. In addition of significantly fewer intraepithelial nerves in the airways of O3/HDMA monkeys compared to FA monkeys, airways of O3/HDMA monkeys contained clusters of abnormal PGP 9.5-immunoreactive cells. Treatment with BUD did not promote re-innervation of epithelial mucosa. In addition, there was a significant increase in PGP 9.5-positive ciliated cells.