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DOI: 10.1160/TH14-01-0053
The coagulation system and its function in early immune defense
Publication History
Received:
18 January 2014
Accepted after minor revision:
18 February 2014
Publication Date:
04 December 2017 (online)
Summary
Blood coagulation has a Janus-faced role in infectious diseases. When systemically activated, it can cause serious complications associated with high morbidity and mortality. However, coagulation is also part of the innate immune system and its local activation has been found to play an important role in the early host response to infection. Though the latter aspect has been less investigated, phylogenetic studies have shown that many factors involved in coagulation have ancestral origins which are often combined with anti-microbial features. This review gives a general overview about the most recent advances in this area of research also referred to as immunothrombosis.
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References
- 1 Versteeg HH. et al. New fundamentals in haemostasis. Physiol Rev 2013; 93: 327-358.
- 2 Tang YQ. et al. Antimicrobial peptides from human platelets. Infect Immun 2002; 70: 6524-6533.
- 3 Frick IM. et al. The contact system--a novel branch of innate immunity generating antibacterial peptides. Embo J 2006; 25: 5569-5578.
- 4 Kirschenbaum LA. et al. Importance of platelets and fibrinogen in neutrophilendothelial cell interactions in septic shock. Crit Care Med 2004; 32: 1904-1909.
- 5 Shpacovitch V. et al. Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity. J Leukoc Biol 2008; 83: 1309-1322.
- 6 Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013; 13: 34-45.
- 7 van der Poll T, Levi M. Crosstalk between inflammation and coagulation: the lessons of sepsis. Curr Vasc Pharmacol 2012; 10: 632-638.
- 8 Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369: 840-851.
- 9 Breitenstein A. et al. Tissue factor: beyond coagulation in the cardiovascular system. Clin Sci 2010; 118: 159-172.
- 10 Rao LV, Pendurthi UR. Regulation of tissue factor coagulant activity on cell surfaces. J Thromb Haemost 2012; 10: 2242-2253.
- 11 Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA 1990; 87: 6934-6938.
- 12 Aberg M, Siegbahn A. Tissue factor non-coagulant signalling - molecular mechanisms and biological consequences with a focus on cell migration and apoptosis. J Thromb Haemost 2013; 11: 817-825.
- 13 Rottingen JA. et al. Binding of human factor VIIa to tissue factor induces cytosolic Ca2+ signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor. J Biol Chem 1995; 270: 4650-4660.
- 14 van den Hengel LG, Versteeg HH. Tissue factor signalling: a multi-faceted function in biological processes. Front Biosci 2011; 3: 1500-1510.
- 15 Camerer E. et al. Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000; 97: 5255-5260.
- 16 van den Berg YW. et al. Alternatively spliced tissue factor induces angiogenesis through integrin ligation. Proc Natl Acad Sci USA 2009; 106: 19497-19502.
- 17 Chu AJ. Tissue factor mediates inflammation. Arch Biochem Biophys 2005; 440: 123-132.
- 18 Srinivasan R, Bogdanov VY. Splice variants of Tissue Factor and integrin-mediated signalling. Thromb Res 2012; 129 (Suppl. 02) S34-37.
- 19 Luo D. et al. Protective roles for fibrin, tissue factor, plasminogen activator inhibitor-1, and thrombin activatable fibrinolysis inhibitor, but not factor XI, during defense against the gram-negative bacterium Yersinia enterocolitica. J Immunol 2011; 187: 1866-1876.
- 20 Papareddy P. et al. C-terminal peptides of tissue factor pathway inhibitor are novel host defense molecules. J Biol Chem 2010; 285: 28387-28398.
- 21 Papareddy P. et al. Tissue factor pathway inhibitor 2 is found in skin and its C-terminal region encodes for antibacterial activity. PLoS One 2012; 7: e52772.
- 22 Chand HS. et al. Structure, function and biology of tissue factor pathway inhibitor-2. Thromb Haemost 2005; 94: 1122-1130.
- 23 Hisaka T. et al. Expression of tissue factor pathway inhibitor-2 in murine and human liver regulation during inflammation. Thromb Haemost 2004; 91: 569-575.
- 24 Opal SM, Esmon CT. Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Crit Care 2003; 7: 23-38.
- 25 Nickel KF, Renne T. Crosstalk of the plasma contact system with bacteria. Thromb Res 2012; 130 (Suppl. 01) S78-83.
- 26 Frick IM. et al. The dual role of the contact system in bacterial infectious disease. Thromb Haemost 2007; 98: 497-502.
- 27 Leeb-Lundberg LM. et al. International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 2005; 57: 27-77.
- 28 Monteiro AC. et al. Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type 1 immunity in a mouse model of subcutaneous infection by Trypanosoma cruzi. J Immunol 2006; 177: 6325-6335.
- 29 Passos GF. et al. Kinin B1 receptor up-regulation after lipopolysaccharide administration: role of proinflammatory cytokines and neutrophil influx. J Immunol 2004; 172: 1839-1847.
- 30 Nordahl EA. et al. Domain 5 of high molecular weight kininogen is antibacterial. J Biol Chem 2005; 280: 34832-34839.
- 31 Cagliani R. et al. Evolutionary analysis of the contact system indicates that kininogen evolved adaptively in mammals and in human populations. Mol Biol Evol 2013; 30: 1397-1408.
- 32 Hoffman M, Monroe DM 3rd. A cell-based model of haemostasis. Thromb Haemost 2001; 85: 958-965.
- 33 Dahlback B, Villoutreix BO. Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol 2005; 25: 1311-1320.
- 34 Shrivastava S. et al. The interface between coagulation and immunity. Am J Transpl 2007; 7: 499-506.
- 35 Esmon CT. Protein C anticoagulant system--anti-inflammatory effects. Semin Immunopathol 2012; 34: 127-132.
- 36 Xu J. et al. Extracellular histones are major mediators of death in sepsis. Nat Med 2009; 15: 1318-1321.
- 37 Williams SC. After Xigris, researchers look to new targets to combat sepsis. Nat Med 2012; 18: 1001.
- 38 Kasetty G. et al. The C-terminal sequence of several human serine proteases encodes host defense functions. J Innate Immun 2011; 3: 471-482.
- 39 Kalle M. et al. Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis. PLoS One 2012; 7: e51313.
- 40 Krem MM, Di Cera E. Evolution of enzyme cascades from embryonic development to blood coagulation. Trends Biochem Sci 2002; 27: 67-74.
- 41 Hanington PC, Zhang SM. The primary role of fibrinogen-related proteins in invertebrates is defense, not coagulation. J Innate Immun 2011; 3: 17-27.
- 42 Pahlman LI. et al. Antimicrobial activity of fibrinogen and fibrinogen-derived peptides--a novel link between coagulation and innate immunity. Thromb Haemost 2013; 109: 930-939.
- 43 Forsyth CB. et al. Integrin alpha(M)beta(2)-mediated cell migration to fibrinogen and its recognition peptides. J Exp Med 2001; 193: 1123-1133.
- 44 Loof TG. et al. Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense. Blood 2011; 118: 2589-2598.
- 45 Burnier L. et al. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost 2009; 101: 439-451.
- 46 Norling LV, Dalli J. Microparticles are novel effectors of immunity. Curr Opin Pharmacol 2013; 13: 570-575.
- 47 Berckmans RJ. et al. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 2001; 85: 639-646.
- 48 Oehmcke S. et al. Stimulation of blood mononuclear cells with bacterial virulence factors leads to the release of pro-coagulant and pro-inflammatory micro-particles. Cell Microbiol 2012; 14: 107-119.
- 49 Sinauridze EI. et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost 2007; 97: 425-434.
- 50 Dasgupta SK. et al. Lactadherin and clearance of platelet-derived microvesicles. Blood 2009; 113: 1332-1339.
- 51 Ramacciotti E. et al. Leukocyte- and platelet-derived microparticles correlate with thrombus weight and tissue factor activity in an experimental mouse model of venous thrombosis. Thromb Haemost 2009; 101: 748-754.
- 52 Jy W. et al. Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation. J Thromb Haemost 2005; 3: 1301-1308.
- 53 Satta N. et al. Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. J Immunol 1994; 153: 3245-3255.
- 54 Wang JG. et al. Levels of microparticle tissue factor activity correlate with coagulation activation in endotoxemic mice. J Thromb Haemost 2009; 7: 1092-1098.
- 55 Aras O. et al. Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood 2004; 103: 4545-4553.
- 56 Nieuwland R. et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95: 930-935.
- 57 Soriano AO. et al. Levels of endothelial and platelet microparticles and their interactions with leukocytes negatively correlate with organ dysfunction and predict mortality in severe sepsis. Crit Care Med 2005; 33: 2540-2546.
- 58 Mostefai HA. et al. Circulating microparticles from patients with septic shock exert protective role in vascular function. Am J Respir Crit Care Med 2008; 178: 1148-1155.
- 59 Delabranche X. et al. Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy. Intensive Care Med 2013; 39: 1695-1703.
- 60 Mortaza S. et al. Detrimental hemodynamic and inflammatory effects of micro-particles originating from septic rats. Crit Care Med 2009; 37: 2045-2050.
- 61 Mastronardi ML. et al. Circulating microparticles from septic shock patients exert differential tissue expression of enzymes related to inflammation and oxidative stress. Crit Care Med 2011; 39: 1739-1748.
- 62 Zafrani L. et al. Calpastatin controls polymicrobial sepsis by limiting procoagulant microparticle release. Am J Respir Crit Care Med 2012; 185: 744-755.
- 63 Oehmcke S. et al. A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. PLoS Pathog 2013; 9: e1003529.
- 64 Reid VL, Webster NR. Role of microparticles in sepsis. Br J Anaesth 2012; 109: 503-513.
- 65 Perez-Casal M. et al. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood 2005; 105: 1515-1522.
- 66 Perez-Casal M. et al. Microparticle-associated endothelial protein C receptor and the induction of cytoprotective and anti-inflammatory effects. Haematologica 2009; 94: 387-394.
- 67 Perez-Casal M. et al. The clinical and functional relevance of microparticles induced by activated protein C treatment in sepsis. Crit Care 2011; 15: R195.
- 68 Lacroix R, Dignat-George F. Microparticles as a circulating source of procoagulant and fibrinolytic activities in the circulation. Thromb Res 2012; 129 (Suppl. 02) S27-29.
- 69 Borregaard N, Cowland JB. Granules of the human neutrophilic polymorpho-nuclear leukocyte. Blood 1997; 89: 3503-3521.
- 70 Brinkmann V. et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303: 1532-1535.
- 71 Kaplan MJ, Radic M. Neutrophil extracellular traps: double-edged swords of innate immunity. J Immunol 2012; 189: 2689-2695.
- 72 Fuchs TA. et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA 2010; 107: 15880-15885.
- 73 Oehmcke S. et al. Activation of the human contact system on neutrophil extra-cellular traps. J Innate Immun 2009; 1: 225-230.
- 74 Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med 2010; 38 (02) Suppl S26-34.
- 75 Pawlinski R. et al. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia. Blood 2004; 103: 1342-1347.
- 76 Danese S. et al. The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications. Blood 2010; 115: 1121-1130.
- 77 Taylor FB Jr.,. et al. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987; 79: 918-925.
- 78 Taylor FB Jr.,. et al. The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood 2000; 95: 1680-1686.
- 79 Kerschen EJ. et al. Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C. J Exp Med 2007; 204: 2439-2448.
- 80 Kerschen E. et al. Activated protein C targets CD8+ dendritic cells to reduce the mortality of endotoxemia in mice. J Clin Invest 2010; 120: 3167-3178.
- 81 Zheng X. et al. Non-hematopoietic EPCR regulates the coagulation and inflammatory responses during endotoxemia. J Thromb Haemost 2007; 5: 1394-1400.
- 82 Levi M. et al. Bronchoalveolar coagulation and fibrinolysis in endotoxemia and pneumonia. Crit Care Med 2003; 31 (04) Suppl S238-242.
- 83 Gunther A. et al. Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 161: 454-462.
- 84 Choi G. et al. Protein C in pneumonia. Thorax 2005; 60: 705-706.
- 85 Rijneveld AW. et al. Local activation of the tissue factor-factor VIIa pathway in patients with pneumonia and the effect of inhibition of this pathway in murine pneumococcal pneumonia. Crit Care Med 2006; 34: 1725-1730.
- 86 Van Den Boogaard FE. et al. Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti-inflammatory and antimicrobial effects in murine pneumococcal pneumonia. J Thromb Haemost 2011; 9: 122-132.
- 87 Kager LM. et al. Endogenous protein C has a protective role during Gram-negative pneumosepsis (melioidosis). J Thromb Haemost 2013; 11: 282-292.
- 88 Kager LM. et al. Overexpression of activated protein C is detrimental during severe experimental gram-negative sepsis (melioidosis). Crit Care Med 2013; 41: e266-274.
- 89 Schouten M. et al. The endothelial protein C receptor impairs the antibacterial response in murine pneumococcal pneumonia and sepsis. Thromb Haemost 2014; 111: 970-980.
- 90 Kager LM. et al. Overexpression of the endothelial protein C receptor is detrimental during pneumonia-derived gram-negative sepsis (Melioidosis). PLoS Negl Trop Dis 2013; 7: e2306.
- 91 Maas C. et al. The plasma contact system 2.0. Semin Thromb Haemost 2011; 37: 375-381.
- 92 Colucci M, Semeraro N. Thrombin activatable fibrinolysis inhibitor: at the nexus of fibrinolysis and inflammation. Thromb Res 2012; 129: 314-319.
- 93 van der Poll T. et al. Regulatory role of cytokines in disseminated intravascular coagulation. Semin Thromb Haemost 2001; 27: 639-651.
- 94 Levi M. et al. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93: 114-120.
- 95 de Jonge E. et al. Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood 2000; 95: 1124-1129.
- 96 Renckens R. et al. Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia. Arterioscler Thromb Vasc Biol 2004; 24: 483-488.
- 97 van der Poll T. et al. Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 1994; 83: 446-451.
- 98 van der Poll T. et al. Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans. Blood 1997; 89: 3727-3734.
- 99 Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator. J Clin Invest 1996; 97: 2440-2451.
- 100 Renckens R. et al. Plasminogen activator inhibitor type 1 is protective during severe Gram-negative pneumonia. Blood 2007; 109: 1593-1601.
- 101 Lim JH. et al. Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections. Immunity 2007; 27: 349-360.
- 102 Kager LM. et al. Plasminogen activator inhibitor type I contributes to protective immunity during experimental Gram-negative sepsis (melioidosis). J Thromb Haemost 2011; 9: 2020-2028.
- 103 Kager LM. et al. Endogenous alpha2-Antiplasmin Is Protective during Severe Gram-Negative Sepsis (Melioidosis). Am J Respir Crit Care Med 2013; 188: 967-975.
- 104 Renckens R. et al. Endogenous tissue-type plasminogen activator is protective during Escherichia coli-induced abdominal sepsis in mice. J Immunol 2006; 177: 1189-1196.
- 105 Kager LM. et al. Endogenous tissue-type plasminogen activator impairs host defense during severe experimental Gram-negative sepsis (melioidosis)*. Crit Care Med 2012; 40: 2168-2175.
- 106 Mondino A, Blasi F. uPA and uPAR in fibrinolysis, immunity and pathology. Trends Immunol 2004; 25: 450-455.
- 107 Rijneveld AW. et al. Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia. J Immunol 2002; 168: 3507-3511.
- 108 Bergmann S, Hammerschmidt S. Fibrinolysis and host response in bacterial infections. Thromb Haemost 2007; 98: 512-520.
- 109 Renckens R. et al. Absence of thrombin-activatable fibrinolysis inhibitor protects against sepsis-induced liver injury in mice. J Immunol 2005; 175: 6764-6771.
- 110 Bengtson SH. et al. Activation of TAFI on the surface of Streptococcus pyogenes evokes inflammatory reactions by modulating the kallikrein/kinin system. J Innate Immun 2009; 1: 18-28.
- 111 Korhonen TK. et al. Fibrinolytic and coagulative activities of Yersinia pestis. Front Cell Infect Microbiol 2013; 3: 35.