C5 CONVERTASE AND AMPLIFICATION OF LUNG INFLAMMATION

这项研究的目的是获得新的见解之一， 扩增途径，这是关键的诱导和延续 急性肺部炎症反应导致慢性炎症 肺病。 使用已建立的免疫化学技术和新的 我们计划研究C3依赖的C5裂解活性， 在正常仓鼠肺的肺泡里。 这一活动将得到净化 来自支气管肺泡灌洗液的无细胞上清液。 其 相互作用免疫生物学、分子和功能特征 C5将进行研究。 使用特异性抗体和免疫检测 系统，将确定其组成补充成分。 总的来说，所获得的结果将有助于鉴定这种C5转化酶 并确定它是否类似于已知的C5转化酶， 补体系统 使用治疗剂，如promidine 我们将确定肺内C5转化酶介导的 可以防止C5裂解。 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），我们将研究是否 其组成补体成分可以在肺内合成， 从而提供了用于肺内组装 转化酶 C5转化酶通过有限的蛋白水解特异性地切割C5， 因此C5趋化因子的产生过程非常有效。 我们 将研究肺细胞是否可以合成C5， 通过免疫生物反馈机制调节， C3和C5的促炎片段。 C5的合成和释放 肺与正常存在的C5转化酶一起可能 产生趋化因子，诱导PMN流入，从而引发急性 炎症 因此，C5的增加或持续释放可能会 导致急性炎症反应的扩大或持续。 通过对调查的严格和仔细的分析，我们希望获得新的 关于C5裂解活性和C5合成的性质的信息， 因此可以影响C5介导的炎症放大， 肺。 这些信息将直接用于开发新的 诊断和治疗方法，以治疗和预防 慢性和使人衰弱的炎性疾病。

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.