ROLE OF SURFACTANT PROTEIN B IN INNATE AIRWAY DEFENSE

说明（申请人摘要）：表面活性剂蛋白B（SP-B）是必需的 和正常的表面活性物质功能。SP-B能够 重组脂质双层，是融合蛋白。基于这些 SP-B蛋白的氨基酸序列与其它蛋白的氨基酸序列相似性 我们假设SP-B本身具有几种抗菌肽， 抗菌性能。我们实验室获得的初步数据 证明SP-B具有体外抗菌活性。的意义 这一意见有三个方面。首先SP-B仅在哺乳动物中表达， 在肺中，它通过支气管分泌到气道衬里流体中， 细支气管和肺泡上皮细胞在相对高的浓度。 因此，它可能作为局部粘膜免疫的一个组成部分， 这些和其他肺部区域的细菌感染。二、表面活性剂 目前，含有SP-B的替代制剂用于安全治疗 新生儿呼吸窘迫综合征，这样的准备工作不会引起 免疫反应。第三，SP-B易于分离或合成。因此，在本发明中， SP-B有可能安全地用于治疗肺部疾病， 细菌感染SP-B在预防或根除细菌生长中的用途 气道在囊性纤维化（CF）中特别重要，其中 由于持续的细菌感染而发生进行性肺损伤。 此外，我们还发现支气管肺泡灌洗液（BAL）中SP-B的异常形式。 成熟的SP-B可能被降解或修饰。我们将 测试SP-B是先天性肺免疫的一个组成部分的假设， 系统，保护人体呼吸道免受细菌感染， CF患者的气道中的活性可能受到损害。这样做的目的是 建议：（1）从BAL中检测SP-B的分子形式和活性， CF患者与正常人的比较，2）描绘气道中的部位 在SP-B被发现的地方，它可能起防御作用，3） 研究SP-B的体外抗菌活性; 含有天然或合成SP-B的抗菌制剂 体内的代理商。从拟议的实验结果将奠定基础 SP-B用于根除细菌性肺部感染的治疗用途。

DESCRIPTION (Applicant's Abstract): Surfactant protein B (SP-B) is essential for postnatal survival and normal surfactant function. SP-B is capable of reorganizing lipid bilayers and is fusigenic protein. Based on these characteristics and the similarity of SP-B's amino acid sequence to those of several antimicrobial peptides, we hypothesized that SP-B itself has antimicrobial properties. Preliminary data obtained by our laboratory have demonstrated he SP-B has in vitro antibacterial activity. The significance of this observation is three-fold. First SP-B is expressed solely in mammalian lungs where it is secreted into the airway lining fluid by bronchial, bronchiolar and alveolar epithelial cells at relatively high concentrations. For that reason, it may act as a component of local mucosal immunity to prevent bacterial infections in these and other regions of the lung. Second, surfactant replacement preparations containing SP-B are presently used for safe treatment of neonatal respiratory distress syndrome, and such preparations do not elicit immunological responses. Third, SP-B is easily isolated or synthesized. Thus, there is potential for safe therapeutic use of SP-B for treatment of pulmonary bacterial infections. Use of SP-B to prevent or eradicate bacterial growth in the airway would be of particular importance in cystic fibrosis (CF), where progressive lung damage occurs as a result of persistent bacterial infection. Moreover, we have found aberrant forms of SP-B in bronchoalveolar lavage (BAL) of adult CF patients and that mature SP-B may be degraded or modified. We will test the hypothesis that SP-B is a component of the innate pulmonary immune system, protecting the human airway against bacterial infection, and this activity may be compromised in the airways of CF patients. The aims of this proposal are 1) to determine molecular forms and activity of SP-B in BAL from CF patients vs. those of normal humans, 2) to delineate the sites in the airway where SP-B is found and in which it may play a defensive role, 3) to characterize the antibacterial activity of SP-B in vitro, and 4) to develop preparations containing native or synthetic SP-B for use as antibacterial agents in vivo. Results from the proposed experiments will lay the foundation for therapeutic use of SP-B for eradication of bacterial lung infections.