A fine-tuned activation and deactivation of proteases and their inhibitors are involved in the execution of the inflammatory response. The zymogen/proenzyme plasminogen is converted to the serine protease plasmin, a key fibrinolytic factor by plasminogen activators including tissue-type plasminogen activator (tPA). Plasmin is part of an intricate protease network controlling proteins of initial hemostasis/coagulation, fibrinolytic and complement system. Activation of these protease cascades is required to mount a proper inflammatory response. Although best known for its ability to dissolve clots and cleave fibrin, recent studies point to the importance of fibrin-independent functions of plasmin during acute inflammation and inflammation resolution. In this review, we provide an up-to-date overview of the current knowledge of the enzymatic and cytokine-like effects of tPA and describe the role of tPA and plasminogen receptors in the regulation of the inflammatory response with emphasis on the cytokine storm syndrome such as observed during coronavirus disease 2019 or macrophage activation syndrome. We discuss tPA as a modulator of Toll like receptor signaling, plasmin as an activator of NFkB signaling, and summarize recent studies on the role of plasminogen receptors as controllers of the macrophage conversion into the M2 type and as mediators of efferocytosis during inflammation resolution.

蛋白酶及其抑制剂的微调激活和失活参与炎症反应的执行。酶原/酶原纤溶酶原通过纤溶酶原激活剂（包括组织型纤溶酶原激活剂 (tPA)）转化为丝氨酸蛋白酶纤溶酶，这是一种关键的纤溶因子。纤溶酶是控制初始止血/凝血、纤溶和补体系统蛋白质的复杂蛋白酶网络的一部分。这些蛋白酶级联的激活是产生适当的炎症反应所必需的。尽管纤溶酶以其溶解血栓和裂解纤维蛋白的能力而闻名，但最近的研究指出了纤溶酶在急性炎症和炎症消退过程中独立于纤维蛋白的功能的重要性。在这篇综述中，我们提供了关于 tPA 酶促和细胞因子样作用的最新知识，并描述了 tPA 和纤溶酶原受体在炎症反应调节中的作用，重点是细胞因子风暴综合征例如在 2019 年冠状病毒病或巨噬细胞激活综合征期间观察到的情况。我们讨论了 tPA 作为 Toll 样受体信号传导的调节剂，纤溶酶作为 NFkB 信号传导的激活剂，并总结了最近关于纤溶酶原受体作为巨噬细胞转化为 M2 型的控制器和炎症消退过程中胞吞作用介质的作用的研究。