ALVEOLAR MACROPHAGE RESPONSE TO CHRONIC STIMULATION

铜绿假单胞菌慢性肺部感染及相关 呼吸道阻塞是囊性肺疾病病理生理学的主要因素， 纤维化（CF）。 高频率的感染与正常的 非致病性微生物尚未得到解释。 由于难以 在从患病患者获得重复的肺灌洗材料时， 还没有对体液和细胞的连续研究， 对慢性刺激的反应。 提供一种实验方法， 这样的连续分析，我们已经适应了琼脂糖珠的方法， 诱导猫慢性假性肺部感染。一种独特的 使用猫的优点是动物的大小，允许顺序 通过支气管灌洗取样。 该模型显示了与 CF包括肺的病理变化以及肺纤维化的获得。 先前证实的假单胞菌特异性吞噬抑制活性 CF患者中。 该提案旨在调查系统性和 肺宿主对慢性刺激的反应。 肺炎性 细胞反应将被定量，肺泡巨噬细胞形态和 根据暴露于假单胞菌的持续时间评价功能 微生物相比，暴露于慢性刺激物（琼脂糖珠）。 将鉴定免疫球蛋白和假单胞菌外产物， 在感染猫的支气管冲洗液中定量。 最后 将采用生物化学和免疫化学技术相结合 从感染猫的血清中纯化并表征抑制剂。 除了研究宿主对假性肺动脉炎的反应外， 感染，这个模型将提供一个有用的方法来回答问题， 对慢性非微生物刺激的连续细胞反应。

Chronic pulmonary infection with Pseudomonas aeruginosa, and associated airway obstruction are major factors in the pathophysiology of cystic fibrosis (CF). The high frequency of infection with a normally non-pathogenic organism has not been explained. Because of the difficulty in obtaining repeated lung lavage material from diseased patients, sequential studies have not been carried out on the humoral and cellular responses to chronic stimulation. To provide an experimental approach for such sequential analysis, we have adapted the agarose bead method of inducing chroninic pseudomonas pulmonary infection to the cat. A distinct advantage in using the cat is the size of the animal, allowing sequential sampling by bronchial lavage. This model has demonstrated similarities to CF including pathological changes in the lung as well as acquisition of the pseudomonas specific phagocytic inhibitory activity previously demonstrated in CF patients. This proposal is designed to investigate systemic and pulmonary host response to chronic stimulation. The pulmonary inflammatory cell response will be quantified and alveolar macrophage morphology and function evaluated with reference to duration of exposure to pseudomonas organisms as compared to exposure to a chronic irritant (agarose beads). Immunoglobulins and pseudomonas exoproducts will be identified and quantified in bronchial washings from infected cats. Finally, a combination of biochemical and immunochemical techniques will be employed to purify and characterize the inhibitory from the serum of infected cats. In addition to investigating the host response to pseudomonas pulmonary infection, this model will provide a useful approach to answer questions on the sequential cellular response to chronic non-microbial stimulation.