Elsevier

Cellular Signalling

Volume 75, November 2020, 109761
Cellular Signalling

Review
The multifaceted role of plasminogen in inflammation

https://doi.org/10.1016/j.cellsig.2020.109761Get rights and content
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open access

Highlights

  • The fibrinolytic factor plasmin interconnects with the coagulation and complement system.

  • Plasmin modulates macrophage functions: migration, phagocytosis.

  • Tissue-type plasminogen activator via LRP1 modulates TLR function.

  • Plasminogen/plasmin regulate efferocytosis and macrophage M1/M2 polarization during inflammation resolution.

  • Plasmin inhibition can suppress the cytokine storm syndrome associated with macrophage activation syndrome.

Abstract

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.

Keywords

Plasminogen
Plasmin
Plasminogen receptor
Matrix metalloproteinase
LRP1
Toll like recepotor
Cytokine storm syndrome
Cytokine
tPA
COVID-19
DIC
Coagulation
Complement
Macrophage activation syndrome
NFkB
PAR

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