ALVEOLAR MACROPHAGE RESPONSE TO CHRONIC STIMULATION

铜绿假单胞菌慢性肺部感染及其相关因素 呼吸道阻塞是囊性病变的主要病理生理因素 纤维化(CF)。感染的高频率与正常的 非致病生物尚未得到解释。因为这个困难 在从患者身上反复获得肺灌洗材料的过程中， 对体液和细胞的后续研究尚未展开。 对慢性刺激的反应。为了提供一种实验性的方法 这样的序列分析，我们采用了琼脂糖珠法 引起猫慢性假单胞菌肺部感染。一种独特的 使用猫的优点是动物的大小，允许按顺序 经支气管灌洗取血。该模型已显示出与 Cf包括肺部的病理变化以及获得 先前证实的假单胞菌特异性吞噬抑制活性 在慢性阻塞性肺疾病患者中。这项提案旨在调查系统性和 肺宿主对慢性刺激的反应。肺炎性 细胞反应将被量化，肺泡巨噬细胞形态和 根据接触假单胞菌的时间评价的功能 与长期接触刺激物(琼脂糖珠)相比，生物的毒性更强。 免疫球蛋白和假单胞菌外源产物将被鉴定和 在感染猫的支气管冲洗液中进行了定量检测。最后，一个 将采用生化和免疫化学技术相结合的方法 提纯和鉴定感染猫血清中的抑制物。 除了调查宿主对肺炎假单胞菌的反应 感染，这个模型将提供一种有用的方法来回答关于 细胞对慢性非微生物刺激的顺序反应。

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.