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The multifaceted role of fibrinogen in tissue injury and inflammation

James P. Luyendyk, Jonathan G. Schoenecker and Matthew J. Flick

Abstract

The canonical role of the hemostatic and fibrinolytic systems is to maintain vascular integrity. Perturbations in either system can prompt primary pathological endpoints of hemorrhage or thrombosis with vessel occlusion. However, fibrin(ogen) and proteases controlling its deposition and clearance, including (pro)thrombin, and plasmin(ogen), have powerful roles in driving acute and reparative inflammatory pathways that impact the spectrum of tissue injury, remodeling and repair. Indeed, fibrin(ogen) deposits are a near universal feature of tissue injury, regardless of the nature of the inciting event, including injuries driven by mechanical insult, infection, or immunological derangements. Fibrin can modify multiple aspects of inflammatory cell function by engaging leukocytes through a variety of cellular receptors and mechanisms. Studies on the role of coagulation system activation and fibrin(ogen) deposition in models of inflammatory disease and tissue injury have revealed points of commonality, as well as context-dependent contributions of coagulation and fibrinolytic factors. However, there remains a critical need to define the precise temporal and spatial mechanisms by which fibrinogen-directed inflammatory events may dictate the severity of tissue injury and coordinate the remodeling and repair events essential to restore normal organ function. Current research trends suggest that future studies will give way to the identification of novel hemostatic factor-targeted therapies for a range of tissue injuries and disease.

  • Submitted July 27, 2018.
  • Accepted November 26, 2018.