Department of Experimental Pathology and Oncology, University of Florence, Italy.
Curr Pharm Des. 2011;17(19):1924-43. doi: 10.2174/138161211796718189.
The urokinase plasminogen activator (uPA) and its receptor (uPAR) provide a cell surface integrated multimolecular complex that exerts pleiotropic functions influencing the development of inflammatory, immune, coagulation and fibrinolytic responses. Here we review the evidences indicating a role of the uPA/uPAR system in the regulation of the innate immune system in the inflammation process, of the adaptive immune response, as well as the role of fibrin and fibrin degradation products at the cross-road between coagulation and inflammation. Comparative studies have clearly highlighted the notion that coagulation and immunity are co-regulated and intertwined. The implication is that the vertebrate blood clotting system is evolutionarily by product of the innate immune system, where the blood clotting proteases have diverged from those comprising the complement system. Differences have emerged gradually, as shown by the acquisition of unique protein structures, such as kringle domains and gla (glutammic acid) domains, in order to comply with the increasingly complex vertebrate systems and to defend higher organisms against a range of infections and injuries. Plasminogen activation also controls the formation of complement anaphylotoxins (responsibe for vasodilatation, increase of venular permeability and leukocyte chemotaxis) and of bradykinin (which accounts for vasodilatation, increase of venular permeability and pain) by regulating the plasma contact system. The urokinase plasminogen activator and its cellular receptor, expressed on the surface of human leukocytes, provide a functional unit that, by regulating interaction of leukocytes with extracellular matrix, as well as its degradation, is critical for the migration of leukocytes and for their movement in the damaged tissues.
尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR）提供了一个细胞表面整合的多分子复合物，发挥着多种功能，影响炎症、免疫、凝血和纤维蛋白溶解反应的发展。在这里，我们回顾了表明 uPA/uPAR 系统在炎症过程中调节固有免疫系统、适应性免疫反应的证据，以及纤维蛋白和纤维蛋白降解产物在凝血和炎症交叉点的作用。比较研究清楚地强调了凝血和免疫共同调节和交织的概念。这意味着脊椎动物的凝血系统是先天免疫系统的进化产物，其中凝血蛋白酶已经从构成补体系统的蛋白酶中分化出来。差异逐渐出现，如获得独特的蛋白质结构，如kringle 结构域和 gla（谷氨酸）结构域，以适应日益复杂的脊椎动物系统，并保护高等生物免受一系列感染和损伤。纤溶酶原激活还通过调节血浆接触系统控制补体过敏毒素（负责血管扩张、静脉通透性增加和白细胞趋化性）和缓激肽（负责血管扩张、静脉通透性增加和疼痛）的形成。人白细胞表面表达的尿激酶型纤溶酶原激活物及其细胞受体提供了一个功能单位，通过调节白细胞与细胞外基质的相互作用及其降解，对白细胞的迁移及其在受损组织中的运动至关重要。
