TY - JOUR T1 - Mechanical Stability and Fibrinolytic Resistance of Clots Containing Fibrin, DNA, and Histones JF - Journal of Biological ChemistryJournal of Biological Chemistry Y1 - 2013 A1 - Longstaff, Colin A1 - Varjú, Imre A1 - Sótonyi, Péter A1 - Szabó, László A1 - Krumrey, Michael A1 - Hoell, Armin A1 - Bóta, Attila A1 - Varga, Zoltán A1 - Komorowicz, Erzsébet A1 - Kolev, Krasimir KW - DNA KW - Fibrinolysis KW - Histones KW - Neutrophil KW - Neutrophil Extracellular Trap KW - Tissue Plasminogen Activator (tPA) AB -

Neutrophil extracellular traps are networks of DNA and associated proteins produced by nucleosome release from activated neutrophils in response to infection stimuli and have recently been identified as key mediators between innate immunity, inflammation, and hemostasis. The interaction of DNA and histones with a number of hemostatic factors has been shown to promote clotting and is associated with increased thrombosis, but little is known about the effects of DNA and histones on the regulation of fibrin stability and fibrinolysis. Here we demonstrate that the addition of histone-DNA complexes to fibrin results in thicker fibers (increase in median diameter from 84 to 123 nm according to scanning electron microscopy data) accompanied by improved stability and rigidity (the critical shear stress causing loss of fibrin viscosity increases from 150 to 376 Pa whereas the storage modulus of the gel increases from 62 to 82 pascals according to oscillation rheometric data). The effects of DNA and histones alone are subtle and suggest that histones affect clot structure whereas DNA changes the way clots are lysed. The combination of histones + DNA significantly prolongs clot lysis. Isothermal titration and confocal microscopy studies suggest that histones and DNA bind large fibrin degradation products with 191 and 136 nm dissociation constants, respectively, interactions that inhibit clot lysis. Heparin, which is known to interfere with the formation of neutrophil extracellular traps, appears to prolong lysis time at a concentration favoring ternary histone-DNA-heparin complex formation, and DNase effectively promotes clot lysis in combination with tissue plasminogen activator.

VL - 288 SN - 0021-9258, 1083-351X UR - http://www.jbc.org/content/288/10/6946 IS - 10 JO - J. Biol. Chem. ER - TY - JOUR T1 - Small-angle X-ray scattering experiments and computer simulations to characterise anisotropy of activated carbons prepared from wood JF - CarbonCarbon Y1 - 2011 A1 - András Wacha A1 - Varga, Zoltán A1 - Vainio, Ulla A1 - Hoell, Armin A1 - Bóta, Attila VL - 49 SN - 00086223 UR - http://linkinghub.elsevier.com/retrieve/pii/S0008622311003988 IS - 12 ER - TY - JOUR T1 - A Closer Look at the Structure of Sterically Stabilized Liposomes: A Small-Angle X-ray Scattering Study JF - The Journal of Physical Chemistry BThe Journal of Physical Chemistry B Y1 - 2010 A1 - Varga, Zoltán A1 - Berényi, Szilvia A1 - Szokol, Bálint A1 - Őrfi, László A1 - Kéri, György A1 - Peták, István A1 - Hoell, Armin A1 - Bóta, Attila VL - 114 SN - 1520-6106, 1520-5207 UR - http://pubs.acs.org/doi/abs/10.1021/jp9109207 IS - 20 JO - A Closer Look at the Structure of Sterically Stabilized Liposomes ER -