C5 CONVERTASE AND AMPLIFICATION OF LUNG INFLAMMATION

这项研究的目的是获得对一个新的见解 在诱导和永久化中起关键作用的放大通路 急性肺炎性反应导致慢性炎症 肺部疾病。使用成熟的免疫化学技术和新的 我们计划研究目前依赖C3的C5裂解活性的方法 在正常仓鼠肺的肺泡内。此活动将被提纯 从支气管肺泡灌洗液的无细胞上清液中提取。它的 相互作用的免疫生物学、分子和功能特征 将对C5进行研究。使用特定的抗体和免疫检测 系统，其组成补充性成分将被确定。 总而言之，所获得的结果将有助于鉴定这种C5转换酶 并确定它是否类似于已知的 补充制。使用普鲁西丁等治疗剂 我们将确定肺内C5转换酶是否介导 C5裂解是可以防止的。 使用C14氨基酸和分离的肺细胞(肺泡巨噬细胞和 肺泡II型肺泡上皮细胞)我们将调查 其组成补体成分可以在肺内合成， 从而为肺内组装提供了一种有效的手段 转化酶。C5转换酶通过有限的蛋白分解特异性地裂解C5， 因此，C5趋化因子的产生过程是非常有效的。我们 研究肺细胞合成C5是否可以 通过免疫生物学反馈机制调节的存在 C3和C5的致炎片段。C5在体内的合成和释放 肺与正常存在的C5转换酶一起很可能 产生趋化因子，诱导中性粒细胞内流，从而启动急性 发炎。因此，C5的增加或继续释放可能会 导致急性炎症反应的放大或持续。 通过对调查的严格和仔细的分析，我们希望获得新的 有关C5裂解活性和C5合成的性质的信息， 从而影响C5介导的炎症放大 阿龙。这些信息将直接应用于开发新的 用于治疗和预防的诊断和治疗方式 慢性和衰弱的炎症性疾病。

The purpose of this study is to gain new insights into one of the amplification pathways that is pivotal in induction and perpetuation of acute pulmonary inflammatory reactions resulting in chronic inflammatory lung disease. Using established immunochemical techniques and novel approaches we plan to study the C3 dependent C5 cleaving activity present within the alveoli of normal hamster lungs. This activity will be purified from cell free supernatants of Bronchoalveolar lavage fluid. Its immunobiological, molecular and functional characteristics for interaction with C5 will be studied. Using specific antibodies and immunodetection systems, its constituent complement components will be identified. Collectively, the results obtained will help identify this C5 convertase and to determine if it is analogous to known C5 convertases of the complement system. Using therapeutic agents such as promidine isothiocyanate we will determine if intrapulmonary C5 convertase mediated C5 cleaving could be prevented. Using C14-amino acids and isolated lung cells (alveolar macrophages and alveolar Type II alveolar epithelial cells) we shall investigate whether its constituent complement components could be synthesized within the lung, thus providing an efficient means for the intrapulmonary assembly of the convertase. C5 convertase cleaves C5 specifically by limited proteolysis, thus the process of C5 chemotactic factor generation is very efficient. We shall investigate whether synthesis of C5 by the lung cells can be modulated via immunobiological feedback mechanism by presence of proinflammatory fragments of C3 and C5. Synthesis and release of C5 within the lung in conjunction with normally present C5 convertase is likely to generate chemotactic factors, induce PMN influx and thus initiate acute inflammation. An increase or continued release of C5 is thus likely to result in amplification or perpetuation of acute inflammatory reactions. By rigorous and careful analysis of the investigations we hope to gain new information regarding nature of C5 cleaving activity and C5 synthesis, could thus affecting C5 mediated amplification of inflammation in the lung. Such information will have direct application towards developing new diagnostic and therapeutic modalities for treatment and prevention of chronic and debilitating inflammatory diseases.