Syrovets T, Simmet Th
Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Helmholtzstr. 20, 89081 Ulm, Germany.
Cell Mol Life Sci. 2004 Apr;61(7-8):873-85. doi: 10.1007/s00018-003-3348-5.
The serine protease plasmin is distributed throughout the human body in the form of the zymogen plasminogen. The plasminogen activation system is mostly recognized for its fibrinolytic activity but is also upregulated in chronic inflammatory diseases, including atherosclerosis and arthritis. Plasmin can bind to a variety of cells, including monocytes, through low-affinity binding sites and triggers aggregation of neutrophils, platelet degranulation and arachidonate release from endothelial cells. In monocytes, plasmin elicits full-scale proinflammatory activation, including lipid mediator release, chemotaxis and cytokine expression, as well as induction of other proinflammatory genes. The effects of plasmin are specific, require the active catalytic center and can be antagonized by lysine analogues, implying binding of the plasmin molecule to the cell membrane through its lysine binding sites. In view of the upregulation of the fibrinolytic genes in chronic inflammatory diseases, cell activation by plasmin is likely to play a major pathophysiological role, a view that is further supported by data from transgenic mice.
丝氨酸蛋白酶纤溶酶以纤溶酶原的酶原形式分布于人体全身。纤溶酶原激活系统主要因其纤维蛋白溶解活性而为人所知，但在包括动脉粥样硬化和关节炎在内的慢性炎症性疾病中也会上调。纤溶酶可通过低亲和力结合位点与包括单核细胞在内的多种细胞结合，并触发中性粒细胞聚集、血小板脱颗粒以及内皮细胞释放花生四烯酸。在单核细胞中，纤溶酶引发全面的促炎激活，包括脂质介质释放、趋化性和细胞因子表达，以及其他促炎基因的诱导。纤溶酶的作用具有特异性，需要活性催化中心，并且可被赖氨酸类似物拮抗，这意味着纤溶酶分子通过其赖氨酸结合位点与细胞膜结合。鉴于慢性炎症性疾病中纤维蛋白溶解基因的上调，纤溶酶介导的细胞激活可能起主要病理生理作用，转基因小鼠的数据进一步支持了这一观点。
