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Title: Cell-Free DNA Promotes Thrombin Autolysis and Generation of Thrombin-Derived C-Terminal Fragments
Authors: Saravanan, Rathi
Choong, Yeu Khai 
Lim, Chun Hwee
Lim, Li Ming
Petrlova, Jitka
Schmidtchen, Artur
Keywords: antimicrobial peptides
cell-free DNA (cfDNA)
host defense peptides
molecular innate immunity
NETs (neutrophil extracellular traps)
Issue Date: 24-Feb-2021
Publisher: Frontiers Media S.A.
Citation: Saravanan, Rathi, Choong, Yeu Khai, Lim, Chun Hwee, Lim, Li Ming, Petrlova, Jitka, Schmidtchen, Artur (2021-02-24). Cell-Free DNA Promotes Thrombin Autolysis and Generation of Thrombin-Derived C-Terminal Fragments. Frontiers in Immunology 12 : 593020. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Cell-free DNA (cfDNA) is the major structural component of neutrophil extracellular traps (NETs), an innate immune response to infection. Antimicrobial proteins and peptides bound to cfDNA play a critical role in the bactericidal property of NETs. Recent studies have shown that NETs have procoagulant activity, wherein cfDNA triggers thrombin generation through activation of the intrinsic pathway of coagulation. We have recently shown that thrombin binds to NETs in vitro and consequently can alter the proteome of NETs. However, the effect of NETs on thrombin is still unknown. In this study, we report that DNA binding leads to thrombin autolysis and generation of multiple thrombin-derived C-terminal peptides (TCPs) in vitro. Employing a 25-residue prototypic TCP, GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), we show that TCPs bind NETs, thus conferring mutual protection against nuclease and protease degradation. Together, our results demonstrate the complex interplay between coagulation, NET formation, and thrombin cleavage and identify a previously undisclosed mechanism for formation of TCPs. © Copyright © 2021 Saravanan, Choong, Lim, Lim, Petrlova and Schmidtchen.
Source Title: Frontiers in Immunology
ISSN: 1664-3224
DOI: 10.3389/fimmu.2021.593020
Rights: Attribution 4.0 International
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