Networks that stop the flow: A fresh look at fibrin and neutrophil extracellular traps

Metchnikoff, 1905 Ehrlich, 1880, Methodologische Beiträge zur Physiologie und Pathologie der verschiedenen Formen der Leukocyten, Z. Klin. Med., 1, 553 Brinkmann, 2004, Neutrophil extracellular traps kill bacteria, Science, 303, 1532, 10.1126/science.1092385 Brinkmann, 2018, Neutrophil extracellular traps in the second decade, J Innate Immun., 10, 414, 10.1159/000489829 Nauseef, 2016, Pondering neutrophil extracellular traps with healthy skepticism, Cell. Microbiol., 18, 1349, 10.1111/cmi.12652 Fuchs, 2007, Novel cell death program leads to neutrophil extracellular traps, J. Cell Biol., 176, 231, 10.1083/jcb.200606027 Kenny, 2017, Diverse stimuli engage different neutrophil extracellular trap pathways, Elife., 6, 10.7554/eLife.24437 Sollberger, 2018, Neutrophil extracellular traps: the biology of chromatin externalization, Dev. Cell, 44, 542, 10.1016/j.devcel.2018.01.019 Hakkim, 2011, Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular trap formation, Nat. Chem. Biol., 7, 75, 10.1038/nchembio.496 Bianchi, 2009, Restoration of NET formation by gene therapy in CGD controls aspergillosis, Blood., 114, 2619, 10.1182/blood-2009-05-221606 Neeli, 2013, Opposition between PKC isoforms regulates histone deimination and neutrophil extracellular chromatin release, Front. Immunol., 4, 38, 10.3389/fimmu.2013.00038 Romani, 2008, Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease, Nature, 451, 211, 10.1038/nature06471 Remijsen, 2009, Reconstitution of protection against Aspergillus infection in chronic granulomatous disease (CGD), Blood, 114, 3497, 10.1182/blood-2009-07-233312 Akong-Moore, 2012, Influences of chloride and hypochlorite on neutrophil extracellular trap formation, PLoS One, 7, 10.1371/journal.pone.0042984 Martinod, 2016, Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis, J. Thromb. Haemost., 14, 551, 10.1111/jth.13239 Remijsen, 2011, Neutrophil extracellular trap cell death requires both autophagy and superoxide generation, Cell Res., 21, 290, 10.1038/cr.2010.150 Germic, 2017, Neither eosinophils nor neutrophils require ATG5-dependent autophagy for extracellular DNA trap formation, Immunology, 152, 517, 10.1111/imm.12790 Chapman, 2019, Caught in a trap? Proteomic analysis of neutrophil extracellular traps in rheumatoid arthritis and systemic lupus erythematosus, Front. Immunol., 10, 423, 10.3389/fimmu.2019.00423 Ryan, 2019, To NET or not to NET: current opinions and state of the science regarding the formation of neutrophil extracellular traps, Cell Death Differ., 26, 395, 10.1038/s41418-018-0261-x Fuchs, 2010, Extracellular DNA traps promote thrombosis, Proc. Natl. Acad. Sci. U. S. A., 107, 15880, 10.1073/pnas.1005743107 Döring, 2017, Neutrophil extracellular traps in atherosclerosis and atherothrombosis, Circ. Res., 120, 736, 10.1161/CIRCRESAHA.116.309692 Swystun, 2016, The role of leukocytes in thrombosis, Blood, 128, 753, 10.1182/blood-2016-05-718114 Martinod, 2014, Thrombosis: tangled up in NETs, Blood., 123, 2768, 10.1182/blood-2013-10-463646 Laridan E, Martinod K, De Meyer SF. Neutrophil extracellular traps in arterial and venous thrombosis. Semin. Thromb. Hemost. 2019; 45(1): 86–93. doi: https://doi.org/10.1055/s-0038-1677040. Kapoor, 2018, The role of neutrophils in thrombosis, Thromb. Res., 170, 87, 10.1016/j.thromres.2018.08.005 Brill, 2012, Neutrophil extracellular traps promote deep vein thrombosis in mice, J. Thromb. Haemost., 10, 136, 10.1111/j.1538-7836.2011.04544.x Darbousset, 2012, Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation, Blood, 120, 2133, 10.1182/blood-2012-06-437772 Savchenko, 2014, Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development, J. Thromb. Haemost., 12, 860, 10.1111/jth.12571 de Boer, 2013, Neutrophils, neutrophil extracellular traps and interleukin-17 associate with the organisation of thrombi in acute myocardial infarction, Thromb. Haemost., 109, 290, 10.1160/TH12-06-0425 Mangold, 2015, Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size, Circ. Res., 116, 1182, 10.1161/CIRCRESAHA.116.304944 Ducroux, 2018, Thrombus neutrophil extracellular traps content impair tPA-induced thrombolysis in acute ischemic stroke, Stroke., 49, 754, 10.1161/STROKEAHA.117.019896 Farkas, 2019, Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases, Thromb. Res., 175, 46, 10.1016/j.thromres.2019.01.006 Jiménez-Alcázar, 2017, Host DNases prevent vascular occlusion by neutrophil extracellular traps, Science, 358, 1202, 10.1126/science.aam8897 Engelmann, 2013, Thrombosis as an intravascular effector of innate immunity, Nat Rev Immunol., 13, 34, 10.1038/nri3345 Jenne, 2015, Platelets in inflammation and infection, Platelets, 26, 286, 10.3109/09537104.2015.1010441 Rendu, 2001, The platelet release reaction: granules' constituents, secretion and functions, Platelets, 12, 261, 10.1080/09537100120068170 Weisel, 2017, Fibrin formation, structure and properties, Subcell Biochem., 82, 405, 10.1007/978-3-319-49674-0_13 Urban, 2009, Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans, PLoS Pathog., 5, 10.1371/journal.ppat.1000639 Gould, 2015, Extracellular DNA and histones: double-edged swords in immunothrombosis, J. Thromb. Haemost., 13, S82, 10.1111/jth.12977 Naudin, 2017, Factor XII contact activation, Semin. Thromb. Hemost., 43, 814, 10.1055/s-0036-1598003 Delabranche, 2017, Immunohaemostasis: a new view on haemostasis during sepsis, Ann. Intensive Care, 7, 117, 10.1186/s13613-017-0339-5 Semeraro, 2011, Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4, Blood, 118, 1952, 10.1182/blood-2011-03-343061 Müller, 2009, Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo, Cell., 139, 1143, 10.1016/j.cell.2009.11.001 Vu, 2016, Histidine-rich glycoprotein binds DNA and RNA and attenuates their capacity to activate the intrinsic coagulation pathway, Thromb. Haemost., 115, 89, 10.1160/TH15-04-0336 Noubouossie, 2017, In vitro activation of coagulation by human neutrophil DNA and histone proteins but not neutrophil extracellular traps, Blood., 129, 1021, 10.1182/blood-2016-06-722298 Komissarov, 2011, Effects of extracellular DNA on plasminogen activation and fibrinolysis, J. Biol. Chem., 286, 41949, 10.1074/jbc.M111.301218 Gould, 2015, Cell-free DNA modulates clot structure and impairs fibrinolysis in sepsis, Arterioscler. Thromb. Vasc. Biol., 35, 2544, 10.1161/ATVBAHA.115.306035 Varjú, 2015, DNA, histones and neutrophil extracellular traps exert anti-fibrinolytic effects in a plasma environment, Thromb. Haemost., 113, 1289, 10.1160/TH14-08-0669 Longstaff, 2013, Mechanical stability and fibrinolytic resistance of clots containing fibrin, DNA, and histones, J. Biol. Chem., 288, 6946, 10.1074/jbc.M112.404301 Bustin, 1970, Regions of high and low cationic charge in a lysine-rich histone, J. Biol. Chem., 245, 1458, 10.1016/S0021-9258(18)63257-0 Ginsburg, 1952, The action of some water-soluble poly-alpha-amino acids on fibrinolysis, Science, 116, 15, 10.1126/science.116.3001.15 Biezunski, 1955, The action of poly-lysine on the conversion of fibrinogen into fibrin by coagulase thrombin, Biochem J., 59, 55, 10.1042/bj0590055 Giannitsis, 1974, Role of leukocyte nuclei in blood coagulation, Naturwissenschaften., 61, 690, 10.1007/BF00606530 Pereira, 1994, Histones interact with anionic phospholipids with high avidity; its relevance for the binding of histone-antihistone immune complexes, Clin. Exp. Immunol., 97, 175, 10.1111/j.1365-2249.1994.tb06064.x Qi, 2017, Neutrophil extracellular traps and endothelial dysfunction in atherosclerosis and thrombosis, Front. Immunol., 8, 928, 10.3389/fimmu.2017.00928 Kleine, 1995, Histone-induced damage of a mammalian epithelium: the conductive effect, Am. J. Phys., 268 Xu, 2009, Extracellular histones are major mediators of death in sepsis, Nat. Med., 15, 1318, 10.1038/nm.2053 Saffarzadeh, 2012, Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones, PLoS One, 7, 10.1371/journal.pone.0032366 Michels, 2016, Histones link inflammation and thrombosis through the induction of Weibel-Palade body exocytosis, J. Thromb. Haemost., 14, 2274, 10.1111/jth.13493 Abrams, 2013, Circulating histones are mediators of trauma-associated lung injury, Am. J. Respir. Crit. Care Med., 187, 160, 10.1164/rccm.201206-1037OC Kleine, 1997, Histone-induced damage of a mammalian epithelium: the role of protein and membrane structure, Am. J. Phys., 273, C1925, 10.1152/ajpcell.1997.273.6.C1925 Gamberucci, 1998, Histones and basic polypeptides activate Ca2+/cation influx in various cell types, Biochem. J., 331, 623, 10.1042/bj3310623 Crittenden, 2004, CalDAG-GEFI integrates signaling for platelet aggregation and thrombus formation, Nat. Med., 10, 982, 10.1038/nm1098 Fuchs, 2011, Histones induce rapid and profound thrombocytopenia in mice, Blood., 118, 3708, 10.1182/blood-2011-01-332676 Carestia, 2013, Functional responses and molecular mechanisms involved in histone-mediated platelet activation, Thromb. Haemost., 110, 1035 Gersh, 2009, Fibrin network structure and clot mechanical properties are altered by incorporation of erythrocytes, Thromb. Haemost., 102, 1169, 10.1160/TH09-03-0199 Wohner, 2011, Lytic resistance of fibrin containing red blood cells, Arterioscler. Thromb. Vasc. Biol., 31, 2306, 10.1161/ATVBAHA.111.229088 Whelihan, 2012, Prothrombin activation in blood coagulation: the erythrocyte contribution to thrombin generation, Blood., 120, 3837, 10.1182/blood-2012-05-427856 Semeraro, 2014, Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells, J. Thromb. Haemost., 12, 1697, 10.1111/jth.12677 Barranco-Medina, 2013, Histone H4 promotes prothrombin autoactivation, J. Biol. Chem., 288, 35749, 10.1074/jbc.M113.509786 Ammollo, 2011, Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation, J. Thromb. Haemost., 9, 1795, 10.1111/j.1538-7836.2011.04422.x Healy, 2017, Activated protein C inhibits neutrophil extracellular trap formation in vitro and activation in vivo, J. Biol. Chem., 292, 8616, 10.1074/jbc.M116.768309 Glaser, 1992, Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation, J. Clin. Invest., 90, 2565, 10.1172/JCI116151 Abe H, Okajima K, Okabe H, Takatsuki K, Binder BR. Granulocyte proteases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro. J. Lab. Clin. Med. 1994;123(6):874–81. PubMed PMID: 8201266. Bajzar, 1996, TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex, J. Biol. Chem., 271, 16603, 10.1074/jbc.271.28.16603 Sakharov, 1997, On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B, J. Biol. Chem., 272, 14477, 10.1074/jbc.272.22.14477 Boffa, 2000, Roles of thermal instability and proteolytic cleavage in regulation of activated thrombin-activable fibrinolysis inhibitor, J. Biol. Chem., 275, 12868, 10.1074/jbc.275.17.12868 Das, 2007, Histone H2B as a functionally important plasminogen receptor on macrophages, Blood., 110, 3763, 10.1182/blood-2007-03-079392 Machovich, 1989, An elastase-dependent pathway of plasminogen activation, Biochemistry, 28, 4517, 10.1021/bi00436a059 Plow, 1980, The major fibrinolytic proteases of human leukocytes, Biochim. Biophys. Acta, 630, 47, 10.1016/0304-4165(80)90136-1 Kolev, 1997, Functional evaluation of the structural features of proteases and their substrate in fibrin surface degradation, J. Biol. Chem., 272, 13666, 10.1074/jbc.272.21.13666 Bagoly, 2007, Down-regulation of activated factor XIII by polymorphonuclear granulocyte proteases within fibrin clot, Thromb. Haemost., 98, 359, 10.1160/TH07-02-0098 Wohner, 2012, Modulation of the von Willebrand factor-dependent platelet adhesion through alternative proteolytic pathways, Thromb. Res., 129, e41, 10.1016/j.thromres.2011.11.021 Papareddy, 2010, Proteolysis of human thrombin generates novel host defense peptides, PLoS Pathog., 6, 10.1371/journal.ppat.1000857 Zeng, 2002, Influence of plasminogen deficiency on the contribution of polymorphonuclear leucocytes to fibrin/ogenolysis: studies in plasminogen knock-out mice, Thromb. Haemost., 88, 805, 10.1055/s-0037-1613306 Massberg, 2010, Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases, Nat. Med., 16, 887, 10.1038/nm.2184 Jochum, 1981, Effect of human granulocytic elastase on isolated human antithrombin III, Hoppe Seylers Z Physiol Chem., 362, 103, 10.1515/bchm2.1981.362.1.103 Wohner, 2010, Neutrophil granulocyte-dependent proteolysis enhances platelet adhesion to the arterial wall under high-shear flow, J. Thromb. Haemost., 8, 1624, 10.1111/j.1538-7836.2010.03890.x Moir, 2002, Polymorphonuclear leucocytes have two opposing roles in fibrinolysis, Thromb. Haemost., 87, 1006, 10.1055/s-0037-1613125 Song, 2019, Antimicrobial microwebs of DNA-histone inspired from neutrophil extracellular traps, Adv. Mater., 31 Gould, 2014, Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms, Arterioscler. Thromb. Vasc. Biol., 34, 1977, 10.1161/ATVBAHA.114.304114 Liou, 1995, Nonisotropic enzyme-inhibitor interactions: a novel nonoxidative mechanism for quantum proteolysis by human neutrophils, Biochemistry, 34, 16171, 10.1021/bi00049a032 Liou, 1996, Quantum proteolysis resulting from release of single granules by human neutrophils. A novel, nonoxidative mechanism of extracellular proteolytic activity, J. Immunol., 157, 2624, 10.4049/jimmunol.157.6.2624 Clark RA, Stone PJ, El Hag A, Calore JD, Franzblau C. Myeloperoxidase-catalyzed inactivation of alpha 1-protease inhibitor by human neutrophils. J. Biol. Chem. 1981; 256(7): 3348–3353. Hirose, 2012, Dynamic changes in the expression of neutrophil extracellular traps in acute respiratory infections, Am. J. Respir. Crit. Care Med., 185, 1130, 10.1164/ajrccm.185.10.1130 Ying, 2000, DNA from bronchial secretions modulates elastase inhibition by alpha(1)-proteinase inhibitor and oxidized secretory leukoprotease inhibitor, Am. J. Respir. Cell Mol. Biol., 23, 506, 10.1165/ajrcmb.23.4.3939 Belorgey, 1995, DNA binds neutrophil elastase and mucus proteinase inhibitor and impairs their functional activity, FEBS Lett., 361, 265, 10.1016/0014-5793(95)00173-7 Rao, 1990, Sulfated polysaccharides prevent human leukocyte elastase-induced acute lung injury and emphysema in hamsters, Am. Rev. Respir. Dis., 142, 407, 10.1164/ajrccm/142.2.407 Reeves, 2002, Killing activity of neutrophils is mediated through activation of proteases by K+ flux, Nature., 416, 291, 10.1038/416291a Kolaczkowska, 2015, Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature, Nat. Commun., 6, 6673, 10.1038/ncomms7673 Crawley, 2007, The central role of thrombin in hemostasis, J. Thromb. Haemost., 5, 95, 10.1111/j.1538-7836.2007.02500.x Zhang, 2010, Circulating mitochondrial DAMPs cause inflammatory responses to injury, Nature., 464, 104, 10.1038/nature08780 Cuadrado, 2008, Tissue plasminogen activator (t-PA) promotes neutrophil degranulation and MMP-9 release, J. Leukoc. Biol., 84, 207, 10.1189/jlb.0907606 Sollberger G, Choidas A, Burn GL, Habenberger P, Di Lucrezia R, Kordes S, Menninger S, Eickhoff J, Nussbaumer P, Klebl B, Krüger R, Herzig A, Zychlinsky A. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps. Sci Immunol. 2018;3(26). pii: eaar6689. doi: 10.1126/sciimmunol.aar6689. Papayannopoulos, 2010, Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps, J. Cell Biol., 191, 677, 10.1083/jcb.201006052 Stavrou, 2018, Factor XII and uPAR upregulate neutrophil functions to influence wound healing, J. Clin. Invest., 128, 944, 10.1172/JCI92880 de Bont, 2019, NETosis, complement, and coagulation: a triangular relationship, Cell Mol Immunol., 16, 19, 10.1038/s41423-018-0024-0 Gehrke, 2013, Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing, Immunity., 39, 482, 10.1016/j.immuni.2013.08.004 Marcus, 1977, Superoxide production and reducing activity in human platelets, J. Clin. Invest., 59, 149, 10.1172/JCI108613 Csomós, 2016, Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps, Cell Death Dis., 7, e2332, 10.1038/cddis.2016.200 Kim, 2002, Histone cross-linking by transglutaminase, Biochem. Biophys. Res. Commun., 293, 1453, 10.1016/S0006-291X(02)00393-5 Puszkin, 1985, Catalytic properties of a calmodulin-regulated transglutaminase from human platelet and chicken gizzard, J. Biol. Chem., 260, 16012, 10.1016/S0021-9258(17)36359-7 Ward, 1997, Binding of the von Willebrand factor A1 domain to histone, Thromb. Res., 86, 469, 10.1016/S0049-3848(97)00096-0 Grässle, 2014, von Willebrand factor directly interacts with DNA from neutrophil extracellular traps, Arterioscler. Thromb. Vasc. Biol., 34, 1382, 10.1161/ATVBAHA.113.303016 Tanka-Salamon, 2010, Proteolytic resistance conferred to fibrinogen by von Willebrand factor, Thromb. Haemost., 103, 291, 10.1160/TH09-07-0420 Etulain, 2015, P-selectin promotes neutrophil extracellular trap formation in mice, Blood., 126, 242, 10.1182/blood-2015-01-624023 Kappelmayer, 2017, The interaction of selectins and PSGL-1 as a key component in thrombus formation and cancer progression, Biomed. Res. Int., 2017, 10.1155/2017/6138145 Wu, 2018, Emerging role of high mobility group Box-1 in thrombosis-related diseases, Cell. Physiol. Biochem., 47, 1319 1337, 10.1159/000490818 Loike, 1995, Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene B4, tumor necrosis factor, and formyl-methionyl-leucyl-phenylalanine, J. Exp. Med., 181, 1763, 10.1084/jem.181.5.1763 Lämmermann, 2008, Rapid leukocyte migration by integrin-independent flowing and squeezing, Nature., 453, 51, 10.1038/nature06887 Yu, 2019, Fibrin modulates shear-induced NETosis in sterile occlusive thrombi formed under haemodynamic flow, Thromb. Haemost., 119, 586, 10.1055/s-0039-1678529 Armstrong, 2013, Capture of lipopolysaccharide (endotoxin) by the blood clot: a comparative study, PLoS One, 8, 10.1371/journal.pone.0080192 Longstaff, 2015, Basic mechanisms and regulation of fibrinolysis, J. Thromb. Haemost., 13, S98, 10.1111/jth.12935 Napirei, 2009, Murine serum nucleases—contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1-like 3 (DNase1l3), FEBS J., 276, 1059, 10.1111/j.1742-4658.2008.06849.x Samson, 2009, A nonfibrin macromolecular cofactor for tPA-mediated plasmin generation following cellular injury, Blood., 114, 1937, 10.1182/blood-2009-02-203448 Harvima, 1988, Hydrolysis of histones by proteinases, Biochem. J., 250, 859, 10.1042/bj2500859 Lim, 2018, Thrombin and plasmin alter the proteome of neutrophil extracellular traps, Front. Immunol., 9, 1554, 10.3389/fimmu.2018.01554 Pires, 2016, The architecture of neutrophil extracellular traps investigated by atomic force microscopy, Nanoscale, 8, 14193, 10.1039/C6NR03416K Farrera, 2013, Macrophage clearance of neutrophil extracellular traps is a silent process, J. Immunol., 191, 2647, 10.4049/jimmunol.1300436 Saha, 2011, Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions, Arterioscler. Thromb. Vasc. Biol., 31, 506, 10.1161/ATVBAHA.110.213405 Lam, 2010, Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization, Nature, 465, 478, 10.1038/nature09001 Pieterse, 2017, Neutrophil extracellular traps drive endothelial-to-mesenchymal transition, Arterioscler. Thromb. Vasc. Biol., 37, 1371, 10.1161/ATVBAHA.117.309002 Blomback, 1989, Native fibrin gel networks observed by 3D microscopy, permeation and turbidity, Biochim. Biophys. Acta, 997, 96, 10.1016/0167-4838(89)90140-4 Baradet, 1995, Three-dimensional reconstruction of fibrin clot networks from stereoscopic intermediate voltage electron microscope images and analysis of branching, Biophys. J., 68, 1551, 10.1016/S0006-3495(95)80327-9 Ma, 2017, Structure, mechanics, and instability of fibrin clot infected with Staphylococcus epidermidis, Biophys. J., 113, 2100, 10.1016/j.bpj.2017.09.001 Collet, 2002, A structural and dynamic investigation of the facilitating effect of glycoprotein IIb/IIIa inhibitors in dissolving platelet-rich clots, Circ. Res., 90, 428, 10.1161/hh0402.105095 Macrae, 2018, A fibrin biofilm covers blood clots and protects from microbial invasion, J. Clin. Invest., 128, 3356, 10.1172/JCI98734 Blinc, 1991, Dependence of blood clot lysis on the mode of transport of urokinase into the clot – a magnetic resonance imaging study in vitro, Thromb. Haemost., 65, 549, 10.1055/s-0038-1648188 Kapral, 1966, Clumping of Staphylococcus aureus in the peritoneal cavity of mice, J. Bacteriol., 92, 1188, 10.1128/JB.92.4.1188-1195.1966 Degen, 2007, Fibrin and fibrinolysis in infection and host defense, J. Thromb. Haemost., 5, 24, 10.1111/j.1538-7836.2007.02519.x Ko, 2016, Fibrinogen is at the Interface of host defense and pathogen virulence in Staphylococcus aureus infection, Semin. Thromb. Hemost., 42, 408, 10.1055/s-0036-1579635 Bangham, 1965, The international standard for streptokinase-streptodornase, Bull. World Health Organ., 33, 235 Beiter, 2006, An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps, Curr. Biol., 16, 401, 10.1016/j.cub.2006.01.056 Wartha, 2007, Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps, Cell. Microbiol., 9, 1162, 10.1111/j.1462-5822.2006.00857.x Korhonen, 2015, Fibrinolytic and procoagulant activities of Yersinia pestis and Salmonella enterica, J. Thromb. Haemost., 13, S115, 10.1111/jth.12932 Yun, 2009, Proteolytic inactivation of tissue factor pathway inhibitor by bacterial omptins, Blood., 113, 1139, 10.1182/blood-2008-05-157180 Kaul, 1997, The chlamydial EUO gene encodes a histone H1-specific protease, J. Bacteriol., 179, 5928, 10.1128/jb.179.18.5928-5934.1997 Kasana, 2011, Microbial proteases: detection, production, and genetic improvement, Crit. Rev. Microbiol., 37, 262, 10.3109/1040841X.2011.577029 Petzelbauer, 2005, The fibrin-derived peptide Bbeta15-42 protects the myocardium against ischemia-reperfusion injury, Nat. Med., 11, 298, 10.1038/nm1198 Thammavongsa, 2013, Staphylococcus aureus degrades neutrophil extracellular traps to promote immune cell death, Science., 342, 863, 10.1126/science.1242255 Jin, 2004, Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism, J. Immunol., 172, 1169, 10.4049/jimmunol.172.2.1169 Mölkänen, 2002, Enhanced activation of bound plasminogen on Staphylococcus aureus by staphylokinase, FEBS Lett., 517, 72, 10.1016/S0014-5793(02)02580-2 Herwald, 1998, Activation of the contact-phase system on bacterial surfaces—a clue to serious complications in infectious diseases, Nat. Med., 4, 298, 10.1038/nm0398-298 Bokarewa, 2001, Thrombin generation and mortality during Staphylococcus aureus sepsis, Microb. Pathog., 30, 247, 10.1006/mpat.2000.0425 Kantor, 1965, 1965. Fibrinogen precipitation by streptococcal M protein. 1. Identity of the reactants and stoichiometry of the reaction, J. Exp. Med., 121, 849, 10.1084/jem.121.5.849 Lipinski, 2000, Resistance of cancer cells to immune recognition and killing, Med. Hypotheses, 54, 456, 10.1054/mehy.1999.0876 Heimburger, 1992, Coagulation and fibrinolysis in cancer, Behring Inst. Mitt., 91, 169 Darrah, 2018, Rheumatoid arthritis and citrullination, Curr. Opin. Rheumatol., 30, 72, 10.1097/BOR.0000000000000452 Tanikawa, 2012, Regulation of histone modification and chromatin structure by the p53-PADI4 pathway, Nat. Commun., 3, 676, 10.1038/ncomms1676 Andrade, 2010, Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullination during cell activation, Arthritis Rheum., 62, 1630, 10.1002/art.27439 Slack, 2011, Autodeimination of protein arginine deiminase 4 alters protein-protein interactions but not activity, Biochemistry., 50, 3997, 10.1021/bi200309e Wang, 2009, Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation, J. Cell Biol., 184, 205, 10.1083/jcb.200806072 Christophorou, 2014, Citrullination regulates pluripotency and histone H1 binding to chromatin, Nature., 507, 104, 10.1038/nature12942 Metzler, 2014, A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis, Cell Rep., 8, 883, 10.1016/j.celrep.2014.06.044 Lewis, 2015, Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation, Nat. Chem. Biol., 11, 189, 10.1038/nchembio.1735 Konig, 2016, A critical reappraisal of neutrophil extracellular traps and NETosis mimics based on differential requirements for protein citrullination, Front. Immunol., 7, 461, 10.3389/fimmu.2016.00461 Wen, 2009, Extracellular DNA is required for root tip resistance to fungal infection, Plant Physiol., 151, 820, 10.1104/pp.109.142067 Nakashima, 2002, Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes, J. Biol. Chem., 277, 49562, 10.1074/jbc.M208795200 Spengler, 2015, Release of active peptidyl arginine deiminases by neutrophils can explain production of extracellular citrullinated autoantigens in rheumatoid arthritis synovial fluid, Arthritis Rheumatol., 67, 3135, 10.1002/art.39313 Fuhrmann, 2015, Chemical biology of protein arginine modifications in epigenetic regulation, Chem. Rev., 115, 5413, 10.1021/acs.chemrev.5b00003 Chang, 2015, The W620 polymorphism in PTPN22 disrupts its interaction with peptidylarginine deiminase type 4 and enhances citrullination and NETosis, Arthritis Rheumatol., 67, 2323, 10.1002/art.39215 Zhang, 2012, Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation, Proc. Natl. Acad. Sci. U. S. A., 109, 13331, 10.1073/pnas.1203280109 Nakayama-Hamada, 2008, Citrullinated fibrinogen inhibits thrombin-catalysed fibrin polymerization, J. Biochem., 144, 393, 10.1093/jb/mvn079 Tilvawala, 2018, The rheumatoid arthritis-associated citrullinome, Cell Chem Biol., 25, 691, 10.1016/j.chembiol.2018.03.002 Chang, 2005, The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogenesis of rheumatoid arthritis, Rheumatology (Oxford), 44, 293, 10.1093/rheumatology/keh473 Sørensen, 2001, Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3, Blood., 97, 3951, 10.1182/blood.V97.12.3951 Lande, 2011, Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus, Sci. Transl. Med., 3, 73ra19, 10.1126/scitranslmed.3001180 Koziel, 2014, Citrullination alters immunomodulatory function of LL-37 essential for prevention of endotoxin-induced sepsis, J. Immunol., 192, 5363, 10.4049/jimmunol.1303062 Sorvillo, 2019, Plasma peptidylarginine deiminase IV promotes VWF-platelet string formation and accelerates thrombosis after vessel injury, Circ. Res., 10.1161/CIRCRESAHA.118.314571 György, 2006, Citrullination: a posttranslational modification in health and disease, Int. J. Biochem. Cell Biol., 38, 1662, 10.1016/j.biocel.2006.03.008 McGraw, 1999, Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase, Infect. Immun., 67, 3248, 10.1128/IAI.67.7.3248-3256.1999 Wingrove, 1992, Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis, J. Biol. Chem., 267, 18902, 10.1016/S0021-9258(19)37046-2 Stobernack T, du Teil Espina M, Mulder LM, Palma Medina LM, Piebenga DR, Gabarrini G, Zhao X, Janssen KMJ, Hulzebos J, Brouwer E, Sura T, Becher D, van Winkelhoff AJ, Götz F, Otto A, Westra J, van Dijl JM. A Secreted Bacterial Peptidylarginine Deiminase Can Neutralize Human Innate Immune Defenses. MBio. 2018;9(5). pii: e01704–18. doi: https://doi.org/10.1128/mBio.01704-18. Li, 2010, PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps, J. Exp. Med., 207, 1853, 10.1084/jem.20100239 Zhou, 2017, Spontaneous secretion of the citrullination enzyme PAD2 and cell surface exposure of PAD4 by neutrophils, Front. Immunol., 8, 1200, 10.3389/fimmu.2017.01200 Kubes, 2018, The enigmatic neutrophil: what we do not know, Cell Tissue Res., 371, 399, 10.1007/s00441-018-2790-5 Kovács, 2014, Ambivalent roles of carboxypeptidase B in the lytic susceptibility of fibrin, Thromb. Res., 133, 80, 10.1016/j.thromres.2013.09.017 Henderson, 2016, Zinc promotes clot stability by accelerating clot formation and modifying fibrin structure, Thromb. Haemost., 115, 533, 10.1160/th15-06-0462