LUNG LAVAGE PROCOAGULANTS IN LUNG INJURY AND REPAIR

肺灌洗促凝剂在肺损伤和修复中的作用

• 批准号: 3081992
• 负责人: Steven Idell
• 金额: $ 6.44万
• 依托单位: UNIVERSITY OF TEXAS HLTH CTR AT TYLER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081992
• 关键词: adult respiratory distress syndrome; autoradiography; bleomycin; clotting factor; coagulation factor VII; coagulation factor X; diagnostic respiratory lavage; disease /disorder model; gel electrophoresis; human subject; immunochemistry; inflammation; pulmonary fibrosis /granuloma; thromboplastin; tissue /cell culture

Fibrin deposition commonly accompanies inflammation and may be involved in tissue repair. Coagulation abnormalities, intravascular and extravascular pulmonary fibrin deposition and the early development of pulmonary fibrosis are commonly found in the Adult Respiratory Distress Syndrome (ARDS). ARDS affects 150,000 patients annually and is lethal in half these cases. The participation of coagulation mechanisms in the pathogenesis of ARDS particularly with respect to lung repair and fibrosis is not well defined. A factor X activating procoagulant activity has been found in bronchoalveolar lavage (BAL) from the lungs of patients with ARDS. Similar activity has been found in BAL of marmosets following treatment with bleomycin, an agent which causes acute lung injury followed by pulmonary fibrosis. The purpose of this study is to characterize the origins and properties of BAL procoagulant activity and to define the relationship of BAL procoagulants to acute lung injury. This will be studied in humans and a well characterized animal model of lung injury. Further, we will examine the role of these procoagulants in the development of pulmonary fibrosis following acute lung injury. This proposal addresses the following questions: 1. What are the mechanisms of the activation of factor X in BAL in inflammatory lung disease? 2. Is the factor X activation the major procoagulant activity in ARDS BAL and in other forms of pulmonary inflammation? 3. Is the generation of BAL procoagulant correlated in vivo with physiologic impairment or pulmonary fibrosis in ARDS and bleomycin induced lung injury? 4. Which cells produce the procoagulants in BAL? Immunochemical and functional assays of procoagulant activators of factor X; in particular factor VII and tissue factor, will be used to investigate the mechanism of activation of factor X. Serial studies of patients and experimental animals will help to determine the physiologic importance of the procoagulant factor X activator. Lung cells in culture will be used to study the origins and mechanisms of expression of BAL procoagulants. Information from these studies will contribute to an understanding of the role of coagulation mechanisms in acute lung injury and repair.

纤维蛋白沉积通常伴随炎症，并可能参与 组织修复 血管内和血管外凝血异常 肺纤维蛋白沉积与肺纤维化的早期发展 常见于成人呼吸窘迫综合征（ARDS）。 ARDS 每年影响15万名患者，其中一半是致命的。 的 凝血机制参与急性呼吸窘迫综合征的发病机制 特别是对于肺修复和纤维化的作用还没有很好的定义。 已发现因子X激活促凝血活性， 支气管肺泡灌洗（BAL）从患有ARDS的患者的肺。 类似 活性已被发现在BAL的绒猴治疗后， 博莱霉素，一种引起急性肺损伤， 纤维化 这项研究的目的是描述起源和 BAL促凝血活性的性质，并定义 BAL促凝剂对急性肺损伤的影响。 这将在人类中进行研究， 肺损伤的良好表征的动物模型。 此外，我们将研究 这些促凝剂在肺纤维化发展中的作用 急性肺损伤 这项建议涉及以下方面 问题： 1.什么是激活因子X在BAL中的机制， 炎症性肺病 2.因子X激活是ARDS BAL的主要促凝活性吗 以及其他形式的肺部炎症 3. BAL促凝血剂的产生是否与体内 生理损害或肺纤维化在ARDS和博莱霉素诱导 肺损伤？ 4. BAL中哪些细胞产生促凝血剂？ 促凝血因子激活剂的免疫化学和功能测定 X;特别是因子VII和组织因子，将用于研究 因子X的激活机制。 对患者的系列研究， 实验动物将有助于确定的生理重要性， 促凝血因子X激活剂。 培养中的肺细胞将用于 研究BAL促凝物的来源和表达机制。 这些研究的信息将有助于了解 凝血机制在急性肺损伤和修复中的作用。