Haemostasis and inflammation are tightly interrelated processes involved in the resolution of tissue damage. The formation and dissolution of fibrin meshwork is a key interface of these processes. In recent years, several studies have demonstrated the contribution of specific fibrin structures (fibrin bio-film) in the protection against microbial infection in external blood clots. Oppositely, different bacteria have been shown to enhance their pathogenicity through modulation of fibrin formation and lysis and a number of molecular events have been described for this pathogen-host interaction. Many studies from the past decade provided a sound support for the concept that neutrophil extracellular traps (extracellular DNA expelled from neutrophils and decorated with released neutrophil enzymes and other proteins) form a secondary scaffold -in addition to fibrin- that increases the mechanical and lytic stability of arterial and venous thrombi. Several new data have identified the contact coagulation pathway (factor XII, prekallikrein, high molecular weight kininogen) as a key junction mechanism involved in the control of blood clotting, inflammation, complement system and fibrinolysis. Infection-related activation of factor XII (mediated by polyphosphates) generates fibrin structures that resist the action of the classic fibrinolytic system (tissue-type plasminogen activator, tPA and plasminogen) opposing the direct stimulating effect of polyphosphates on the factor XIIa-mediated plasminogen activation. Overactivation of the contact pathway resulting in overt tissue swelling has been described in non-classic cases of hereditary angioedema related to gain-of-function mutations of factor XII and plasminogen. In contrast, key components of the fibrinolytic system have been reported to attenuate the innate immunity; for example, tPA suppresses the macrophage response to potent inflammatory stimuli (e.g. lipopolysaccharide). tPA-induced immunosuppression could increase the infection risk in clinical settings when therapeutic fibrinolysis is used (e.g. tPA treatment in acute ischemic stroke).
The proposed Research Topic aims to compile state-of-the-art Review and Mini-Review articles that summarize the recent advances in our understanding of the interactions of innate immunity and fibrinolysis focusing on any of the aspects outlined above. The collection will also accept reports of Original Research that advances the knowledge on the role of fibrinolysis in immunity along the following lines:
· infection-related modulation of fibrin structure and lysability
· neutrophil activation and neutrophil extracellular traps in thrombosis
· contact system-dependent molecular mechanisms driving downstream immune response and fibrinolysis
· tPA/plasmin-mediated immunomodulation
The list above is not intended to be exhaustive, reports of any novel, unexpected aspect of the interaction of fibrinolysis and immunity are welcome. Primarily manuscripts that provide essential novel mechanistic insights will be considered for publication.
Haemostasis and inflammation are tightly interrelated processes involved in the resolution of tissue damage. The formation and dissolution of fibrin meshwork is a key interface of these processes. In recent years, several studies have demonstrated the contribution of specific fibrin structures (fibrin bio-film) in the protection against microbial infection in external blood clots. Oppositely, different bacteria have been shown to enhance their pathogenicity through modulation of fibrin formation and lysis and a number of molecular events have been described for this pathogen-host interaction. Many studies from the past decade provided a sound support for the concept that neutrophil extracellular traps (extracellular DNA expelled from neutrophils and decorated with released neutrophil enzymes and other proteins) form a secondary scaffold -in addition to fibrin- that increases the mechanical and lytic stability of arterial and venous thrombi. Several new data have identified the contact coagulation pathway (factor XII, prekallikrein, high molecular weight kininogen) as a key junction mechanism involved in the control of blood clotting, inflammation, complement system and fibrinolysis. Infection-related activation of factor XII (mediated by polyphosphates) generates fibrin structures that resist the action of the classic fibrinolytic system (tissue-type plasminogen activator, tPA and plasminogen) opposing the direct stimulating effect of polyphosphates on the factor XIIa-mediated plasminogen activation. Overactivation of the contact pathway resulting in overt tissue swelling has been described in non-classic cases of hereditary angioedema related to gain-of-function mutations of factor XII and plasminogen. In contrast, key components of the fibrinolytic system have been reported to attenuate the innate immunity; for example, tPA suppresses the macrophage response to potent inflammatory stimuli (e.g. lipopolysaccharide). tPA-induced immunosuppression could increase the infection risk in clinical settings when therapeutic fibrinolysis is used (e.g. tPA treatment in acute ischemic stroke).
The proposed Research Topic aims to compile state-of-the-art Review and Mini-Review articles that summarize the recent advances in our understanding of the interactions of innate immunity and fibrinolysis focusing on any of the aspects outlined above. The collection will also accept reports of Original Research that advances the knowledge on the role of fibrinolysis in immunity along the following lines:
· infection-related modulation of fibrin structure and lysability
· neutrophil activation and neutrophil extracellular traps in thrombosis
· contact system-dependent molecular mechanisms driving downstream immune response and fibrinolysis
· tPA/plasmin-mediated immunomodulation
The list above is not intended to be exhaustive, reports of any novel, unexpected aspect of the interaction of fibrinolysis and immunity are welcome. Primarily manuscripts that provide essential novel mechanistic insights will be considered for publication.