Abstract
Coagulation system is currently considered an integrated part of innate immunity. Clotting activation in response to bacterial surface along with complement cascade priming represents the first line of defense against pathogens. In the last three decades, we learned that several coagulation factors, including factor II or thrombin and factor X, can interact with specific cell surface receptors activated by an unusual proteolytic mechanism and belonging to a novel class of G-protein-coupled receptors known as protease-activated receptors (PARs). PARs are expressed by a variety of cells, including monocytes, dendritic cells, and endothelial cells and may play a key role in the modulation of innate immunity and in the regulation of its interaction with the adaptive branch of the immune system. Also, the fibrinolytic system, in which activation is controlled by coagulation, can interact with innate immunity, and it is a key modulator of extracellular matrix deposition eventually leading to scarring and fibrosis. In the setting of kidney transplantation, coagulation and fibrinolytic systems have been shown to play key roles in the ischemia/reperfusion injury featuring delayed graft function and in the pathogenesis of tissue damage following acute and chronic rejection. In the present review, we aim to describe the mechanisms leading to coagulation and fibrinolysis activation in this setting and their interaction with the priming of the innate immune response and their role in kidney graft rejection.
Highlights
Kidney transplantation is the treatment of choice for most patients with end-stage renal disease because kidney graft recipients live longer than dialysis patients and have a markedly higher quality of life
The tissue damage featuring ischemia/reperfusion in renal transplant recipient is represented by tubular cell apoptosis and interstitial inflammation, a pathogenic event underlying an early posttransplant form of acute kidney injury (AKI) known as delayed graft function (DGF) [45]
Zietek et al demonstrated that organ donors who had injured death, such as road traffic injury, were characterized by an intensive activation of fibrinolytic process when compared with non-injured donors, which showed instead intensive activation of blood coagulation [72]
Summary
Giovanni Stallone 1, Paola Pontrelli 2*, Federica Rascio 1, Giuseppe Castellano 1, Loreto Gesualdo 2 and Giuseppe Grandaliano 3,4. Reviewed by: Kazue Takahashi, Massachusetts General Hospital and Harvard Medical School, United States Mihaela Gadjeva, Harvard Medical School, United States. Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal
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