Thrombin-activatable fibrinolysis inhibitor binds to Streptococcus pyogenes by interacting with collagen-like proteins A and B.

J Biol Chem

Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University, SE-22184 Lund, Sweden.

Published: August 2007

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.

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M610015200DOI Listing

Publication Analysis

Top Keywords

thrombin-activatable fibrinolysis
8
fibrinolysis inhibitor
8
inhibitor binds
4
binds streptococcus
4
streptococcus pyogenes
4
pyogenes interacting
4
interacting collagen-like
4
collagen-like proteins
4
proteins regulation
4
regulation proteolysis
4

Similar Publications

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 PDF

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.

View Article and Find Full Text PDF

Dependence of clot structure and fibrinolysis on apixaban and clotting activator.

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 PDF

Novel Deep Sea Isoindole Alkaloid FGFC1 Exhibits Its Fibrinolytic Effects by Inhibiting Thrombin-Activatable Fibrinolysis Inhibitor.

Pharmaceuticals (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.

View Article and Find Full Text PDF

High-dose atorvastatin and rosuvastatin reduce the levels of neutrophil extracellular trap-related proteins in coronary artery disease: association with prothrombotic state.

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.

Article Synopsis
  • The study aimed to investigate how high-dose statins impact the formation of neutrophil extracellular traps (NETs) in patients with coronary artery disease (CAD).
  • A group of 130 patients was monitored before and after starting statin therapy, revealing significant reductions in proteins linked to NETs, such as citrullinated histone H3, myeloperoxidase, and neutrophil elastase.
  • These reductions correlated with decreased inflammation markers and changes that suggest improved clot formation properties, indicating that statins may have beneficial effects beyond just lowering LDL cholesterol.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!