Wygrecka Malgorzata, Jablonska Ewa, Guenther Andreas, Preissner Klaus T, Markart Philipp
Department of Biochemistry, Faculty of Medicine, University of Giessen Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
Thromb Haemost. 2008 Mar;99(3):494-501. doi: 10.1160/TH07-11-0666.
Acute inflammatory and chronic interstitial lung diseases are characterized by excessive and persistent fibrin deposition in the lung. Intraalveolar fibrin accumulation, observed under these conditions, arises from a leakage of plasma proteins (including fibrinogen) into the alveolar space in combination with a disbalance of alveolar haemostasis. Tissue factor in association with factor VIIa and inhibition of urokinase by plasminogen activator inhibitor-1 are major factors that are responsible for the procoagulant and antifibrinolytic state. In addition, in acute respiratory distress syndrome (ARDS) patients, factor VII-activating protease and extracellular RNA, which may be released into the extracellular milieu from damaged cells during lung injury, may contribute to fibrin formation as well. Fibrin itself can increase vascular permeability, influence the expression of inflammatory mediators and alter the migration and proliferation of various cell types. Additionally, fibrin may inactivate pulmonary surfactant and provide a matrix on which fibroblasts can migrate and produce collagen. Furthermore, cellular activities of haemostatic proteases may also contribute to proinflammatory and fibrotic processes in the lung. The application of coagulation inhibitors, like tissue factor pathway inhibitor, active site-inactivated factor VIIa, activated protein C, antithrombin, heparin or hirudin turned out to be beneficial in experimental models of acute and chronic lung injury. However, the ability of anticoagulant and profibrinolytic agents to improve clinical outcome remains to be elucidated. In the current article, the role of the alveolar coagulation and fibrinolysis systems in acute inflammatory and chronic interstitial lung diseases is discussed with regard to pathomechanisms and modalities of intervention.
急性炎症性和慢性间质性肺疾病的特征是肺内存在过量且持续的纤维蛋白沉积。在这些情况下观察到的肺泡内纤维蛋白积聚，是由于血浆蛋白（包括纤维蛋白原）漏入肺泡腔，同时伴有肺泡止血失衡所致。组织因子与因子VIIa结合以及纤溶酶原激活物抑制剂-1对尿激酶的抑制作用是导致促凝和抗纤溶状态的主要因素。此外，在急性呼吸窘迫综合征（ARDS）患者中，因子VII激活蛋白酶和细胞外RNA（在肺损伤期间可能从受损细胞释放到细胞外环境中）也可能促进纤维蛋白的形成。纤维蛋白本身可增加血管通透性，影响炎症介质的表达，并改变各种细胞类型的迁移和增殖。此外，纤维蛋白可能使肺表面活性物质失活，并提供一个基质，使成纤维细胞能够迁移并产生胶原蛋白。此外，止血蛋白酶的细胞活性也可能促进肺内的促炎和纤维化过程。在急性和慢性肺损伤的实验模型中，应用凝血抑制剂，如组织因子途径抑制剂、活性位点失活的因子VIIa、活化蛋白C、抗凝血酶、肝素或水蛭素，已证明是有益的。然而，抗凝剂和促纤溶药物改善临床结局的能力仍有待阐明。在本文中，将从发病机制和干预方式方面讨论肺泡凝血和纤溶系统在急性炎症性和慢性间质性肺疾病中的作用。
