Regulation of proteolysis is a critical element of the host immune system and plays an important role in the induction of pro- and anti-inflammatory reactions in response to infection. Some bacterial species take advantage of these processes and recruit host proteinases to their surface in order to counteract the host attack. Here we show that Thrombin-activatable Fibrinolysis Inhibitor (TAFI), a zinc-dependent procarboxypeptidase, binds to the surface of group A streptococci of an M41 serotype. The interaction is mediated by the streptococcal collagen-like surface proteins A and B (SclA and SclB), and the streptococcal-associated TAFI is then processed at the bacterial surface via plasmin and thrombin-thrombomodulin. These findings suggest an important role for TAFI in the modulation of host responses by streptococci.
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http://dx.doi.org/10.1074/jbc.M610015200 | DOI Listing |
Thromb Haemost
January 2025
Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Background: Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear.
View Article and Find Full Text PDFRMD Open
December 2024
Rheumatology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
Objectives: To assess the effect of treatment on haemostatic parameters in patients with early rheumatoid arthritis (RA).
Methods: Patients with newly diagnosed RA started methotrexate and were randomised to additional conventional treatment, certolizumab pegol, abatacept or tocilizumab. Several biomarkers for haemostasis were analysed including parameters of the two global haemostatic assays-overall haemostatic potential (OHP) and endogenous thrombin potential (ETP), as well as single haemostatic factors-fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in 24 patients at baseline, 12 and 24 weeks after the start of the treatment.
Res Pract Thromb Haemost
November 2024
Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.
Background: Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that must be broken down (fibrinolysis) to restore blood flow.
View Article and Find Full Text PDFPharmaceuticals (Basel)
October 2024
Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Background: The thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator in the balance between blood clot formation (coagulation) and dissolution (fibrinolysis), which is mainly activated by thrombin bonded with thrombomodulin (TM).
Methods: In this study, the investigation focused on the unique target TAFI of fungi fibrinolytic compound 1 (FGFC1), a novel fibrinolytic compound sourced from the deep sea. In this sense, the regulation of TAFI by FGFC1, in comparison to established TAFI inhibitors such as DS-1040 and PCTI in hPPP, was investigated, which was validated through the molecular docking of FGFC1 to TAFI.
Pol Arch Intern Med
October 2024
Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland; Krakow Center for Medical Research and Technologies, St. John Paul II Hospital, Kraków, Poland.
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