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Extracellular Histones Inhibit Fibrinolysis through Noncovalent and Covalent Interactions with Fibrin

Thromb Haemost. 2020-11; 
Matthew Locke, Colin Longstaff
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Recombinant Antibody Expression … Kingdom). Anti-his tag anti- bodies (A00186) were from Genscript (New Jersey, United States). Mixed histones (calf thymus, IIA) and recombinant peptidyl arginine deiminase 4 (PAD4) were from Sigma (Poole, United Kingdom) … Get A Quote


Histones released into circulation as neutrophil extracellular traps are causally implicated in the pathogenesis of arterial, venous, and microvascular thrombosis by promoting coagulation and enhancing clot stability. Histones induce structural changes in fibrin rendering it stronger and resistant to fibrinolysis. The current study extends these observations by defining the antifibrinolytic mechanisms of histones in purified, plasma, and whole blood systems. Although histones stimulated plasminogen activation in solution, they inhibited plasmin as competitive substrates. Protection of fibrin from plasmin digestion is enhanced by covalent incorporation of histones into fibrin, catalyzed by activated transglutami... More