In vivo activation and functions of the protease factor XII

Jenny Björkqvist; Katrin F. Nickel; Evi Stavrou; Thomas Renné

doi:10.1160/th14-04-0311

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(05): 868-875
DOI: 10.1160/th14-04-0311

Theme Issue Article

Schattauer GmbH

In vivo activation and functions of the protease factor XII

Jenny Björkqvist

¹Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

²Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

,

Katrin F. Nickel

¹Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

²Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

³Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg, Hamburg, Germany

,

Evi Stavrou

⁴Department of Medicine, Hematology and Oncology Division, Case Western Reserve University; Louis Stokes Veterans Administration Hospital; University Hospital Case Medical Center, Cleveland, Ohio, USA

,

Thomas Renné

¹Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

²Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

³Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg, Hamburg, Germany

› Author Affiliations

Abstract

Summary

Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. The biochemistry of the contact system in vitro is well understood; however, its in vivo functions are just beginning to emerge. The current review concentrates on activators and functions of the FXII-driven contact system in vivo. Elucidating its physiologic activities offers the exciting opportunity to develop strategies for the safe interference with both thrombotic and inflammatory diseases.

Keywords

Coagulation factors - contact phase - proteases

Full Text

References

References
1 Renne T. et al. In vivo roles of factor XII. Blood 2012; 120: 4296-4303.
2 Herwald H. et al. Mapping of the discontinuous kininogen binding site of prekallikrein. A distal binding segment is located in the heavy chain domain A4. J Biol Chem 1996; 271: 13061-13067.
3 Renne T. et al. Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2. J Biol Chem 1999; 274: 25777-25784.
4 Muller F, Renne T. Novel roles for factor XII-driven plasma contact activation system. Curr Opin Hematol 2008; 15: 516-521.
5 Bjorkqvist J. et al. Plasma kallikrein: the bradykinin-producing enzyme. Thromb Haemost 2013; 110: 399-407.
6 Stavrou E, Schmaier AH. Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of haemostasis & thrombosis. Thromb Res 2010; 125: 210-215.
7 Renne T. The Factor XII-Driven plasma Contact System. In: Textbook of Haemostasis and Thrombosis - Basic principles and clinical practice. 6th ed.. Lippincott Williams & Wilkins; 2013. pp. 242-53.
8 Cool DE, MacGillivray RT. Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5’-flanking region. J Biol Chem 1987; 262: 13662-13673.
9 Cochrane CG. et al. Activation of Hageman factor in solid and fluid phases. A critical role of kallikrein. J Exp Med 1973; 138: 1564-1583.
10 Samuel M. et al. Human factor XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and ultraviolet difference spectroscopic studies. J Biol Chem 1992; 267: 19691-19697.
11 Pixley RA. et al. The regulation of human factor XIIa by plasma proteinase inhibitors. J Biol Chem 1985; 260: 1723-1729.
12 Siegerink B. et al. Intrinsic coagulation activation and the risk of arterial thrombosis in young women: results from the Risk of Arterial Thrombosis in relation to Oral contraceptives (RATIO) case-control study. Circulation 2010; 122: 1854-1861.
13 de Agostini A. et al. Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor. J Clin Invest 1984; 73: 1542-1549.
14 Maas C, Renne T. Regulatory mechanisms of the plasma contact system. Thromb Res 2012; 129 (Suppl. 02) 73-76.
15 Ratnoff OD, Margolius Jr. A. Hageman trait: an asymptomatic disorder of blood coagulation. Trans Assoc Am Physicians 1955; 68: 149-154.
16 Pauer HU. et al. Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo. Thromb Haemost 2004; 92: 503-508.
17 Renne T. et al. Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med 2005; 202: 271-281.
18 Kleinschnitz C. et al. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischaemia without interfering with haemostasis. J Exp Med 2006; 203: 513-518.
19 Pham M. et al. Enhanced cortical reperfusion protects coagulation factor XII-deficient mice from ischaemic stroke as revealed by high-field MRI. Neuroimage 2010; 49: 2907-2914.
20 Muller F. et al. Factor XI and XII as antithrombotic targets. Curr Opin Hematol 2011; 18: 349-355.
21 Johnson CY. et al. The factor XII -4C>T variant and risk of common thrombotic disorders: A HuGE review and meta-analysis of evidence from observational studies. Am J Epidemiol 2011; 173: 136-144.
22 Girolami A. et al. Rebuttal: factor XII levels, factor XII 46 C>T polymorphism and venous thrombosis: a word of caution is needed. Thromb Haemost 2004; 92: 892-893 author reply 894-895.
23 Bird JE. et al. Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: murine ortholog of the Fletcher trait. Thromb Haemost 2012; 107: 1141-1150.
24 Cheng Q. et al. A role for factor XIIa-mediated factor XI activation in thrombus formation in vivo. Blood 2010; 116: 3981-3989.
25 Salomon O. et al. Reduced incidence of ischaemic stroke in patients with severe factor XI deficiency. Blood 2008; 111: 4113-4117.
26 Salomon O. et al. Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thromb Haemost 2011; 105: 269-273.
27 Doggen CJ. et al. Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: Opposite and synergistic effects of factors XI and XII. Blood 2006; 108: 4045-4051.
28 Iwaki T, Castellino FJ. Plasma levels of bradykinin are suppressed in factor XII-deficient mice. Thromb Haemost 2006; 95: 1003-1010.
29 Schloesser M. et al. Mutations in the human factor XII gene. Blood 1997; 90: 3967-3977.
30 Miyata T. et al. Coagulation factor XII (Hageman factor) Washington D C.: inactive factor XIIa results from Cys-571----Ser substitution. Proc Natl Acad Sci USA 1989; 86: 8319-8322.
31 Hovinga JK. et al. Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallik-rein cleavage site. Blood 1994; 84: 1173-1181.
32 Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med 2008; 359: 1027-1036.
33 Bjorkqvist J. et al. Hereditary angioedema: a bradykinin-mediated swelling disorder. Thromb Haemost 2013; 109: 368-374.
34 Han ED. et al. Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor. J Clin Invest 2002; 109: 1057-1063.
35 Cugno M. et al. Bradykinin and the pathophysiology of angioedema. Int Immunopharmacol 2003; 3: 311-317.
36 Bork K. et al. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet 2000; 356: 213-217.
37 Cichon S. et al. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet 2006; 79: 1098-1104.
38 Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun 2006; 343: 1286-1289.
39 Citarella F. et al. Structure/function analysis of human factor XII using recombinant deletion mutants. Evidence for an additional region involved in the binding to negatively charged surfaces. Eur J Biochem 1996; 238: 240-249.
40 Bork K. et al. A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor. Clin Immunol 2011; 141: 31-35.
41 Kiss N. et al. Novel duplication in the F12 gene in a patient with recurrent angioedema. Clin Immunol 2013; 149: 142-145.
42 Moreno AS. et al. Structural and Molecular Changes Caused By Mutations Thr328Lys and Thr328Arg In FXII Associated With Hereditary Angioedema With Normal C1 Inhibitor. J Allergy Clin Immunol 2014; 133: 39.
43 Maas C. et al. The plasma contact system 2.0. Semin Thromb Haemost 2011; 37: 375-381.
44 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.
45 Davis AE. Hereditary angioedema: a current state-of-the-art review, III: mechanisms of hereditary angioedema. Ann Allergy Asthma Immunol 2008; 100 (Suppl. 02) 7-12.
46 Kaplan AP. Kinins, airway obstruction, and anaphylaxis. Chem Immunol Allergy 2010; 95: 67-84.
47 Oschatz C. et al. Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity 2011; 34: 258-268.
48 MacLaughlin EJ. et al. Anaphylactoid reaction to enoxaparin in a patient with deep venous thrombosis. Pharmacotherapy 2002; 22: 1511-1515.
49 Summers CW. et al. Factors predicting anaphylaxis to peanuts and tree nuts in patients referred to a specialist center. J Allergy Clin Immunol 2008; 121: 632-638e2.
50 Colman RW. et al. Effect of heparin on the inhibition of the contact system enzymes. Ann NY Acad Sci 1989; 556: 95-103.
51 Capila I, Linhardt RJ. Heparin-protein interactions. Angew Chem Int Ed Engl 2002; 41: 391-412.
52 Pixley RA. et al. Effect of heparin on the inactivation rate of human activated factor XII by antithrombin III. Blood 1985; 66: 198-203.
53 Beltrami E, Jesty J. Mathematical analysis of activation thresholds in enzyme-catalyzed positive feedbacks: application to the feedbacks of blood coagulation. Proc Natl Acad Sci USA 1995; 92: 8744-8748.
54 Lombardini C. et al. “Heparinization” and hyperfibrinogenolysis by wasp sting. Am J Emerg Med 2009; 27: 1176e1-3.
55 Mazzi G. et al. Primary hyperfibrinogenolysis in a patient with anaphylactic shock. Haematologica 1994; 79: 283-285.
56 Dlamini Z, Bhoola KD. Upregulation of tissue kallikrein, kinin B1 receptor, and kinin B2 receptor in mast and giant cells infiltrating oesophageal squamous cell carcinoma. J Clin Pathol 2005; 58: 915-922.
57 Ishizaka T. et al. Release of histamine and arachidonate from mouse mast cells induced by glycosylation-enhancing factor and bradykinin. J Immunol 1985; 134: 1880-1887.
58 Johne J. et al. Platelets promote coagulation factor XII-mediated proteolytic cascade systems in plasma. Biol Chem 2006; 387: 173-178.
59 Bjorkqvist J. et al. Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents. Biol Chem 2013; 394: 1195-1204.
60 Maas C. et al. Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation. J Clin Invest 2008; 118: 3208-3218.
61 Renne T. et al. Characterization of the H-kininogen-binding site on factor XI: a comparison of factor XI and plasma prekallikrein. J Biol Chem 2002; 277: 4892-4899.
62 Renne T, Muller-Esterl W. Cell surface-associated chondroitin sulfate proteoglycans bind contact phase factor H-kininogen. FEBS Lett 2001; 500: 36-40.
63 Renne T. et al. Local bradykinin formation is controlled by glycosaminoglycans. J Immunol 2005; 175: 3377-3385.
64 Schmaier AH. The elusive physiologic role of Factor XII. J Clin Invest 2008; 118: 3006-3009.
65 Kishimoto TK. et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med 2008; 358: 2457-2467.
66 Nzeako UC. et al. Hereditary angioedema: a broad review for clinicians. Arch Intern Med 2001; 161: 2417-2429.
67 Bork K. et al. Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol 2009; 124: 129-134.
68 Eikelboom JW, Weitz JI. New anticoagulants. Circulation 2010; 121: 1523-1532.
69 Muller F. et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 2009; 139: 1143-1156.
70 Xu Y. et al. Factor XIIa inhibition by Infestin-4: in vitro mode of action and in vivo antithrombotic benefit. Thromb Haemost 2013; 111: 694-704.
71 Hagedorn I. et al. Factor XIIa inhibitor recombinant human albumin Infestin-4 abolishes occlusive arterial thrombus formation without affecting bleeding. Circulation 2010; 121: 1510-1517.
72 Chen JW. et al. Selective factor XIIa inhibition attenuates silent brain ischaemia: application of molecular imaging targeting coagulation pathway. JACC Cardiovasc Imaging 2012; 5: 1127-1138.
73 Decrem Y. et al. Ir-CPI, a coagulation contact phase inhibitor from the tick Ixodes ricinus, inhibits thrombus formation without impairing haemostasis. J Exp Med 2009; 206: 2381-2395.
74 Yau JW. et al. Corn trypsin inhibitor coating attenuates the prothrombotic properties of catheters in vitro and in vivo. Acta Biomater 2012; 8: 4092-4100.
75 Carter TH. et al. Cabbage seed protease inhibitor: a slow, tight-binding inhibitor of trypsin with activity toward thrombin, activated Stuart factor (factor Xa), activated Hageman factor (factor XIIa), and plasmin. Blood 1990; 75: 108-115.
76 Hojima Y. et al. Pumpkin seed inhibitor of human factor XIIa (activated Hageman factor) and bovine trypsin. Biochemistry 1982; 21: 3741-3746.
77 Ulmer JS. et al. Ecotin is a potent inhibitor of the contact system proteases factor XIIa and plasma kallikrein. FEBS Lett 1995; 365: 159-163.
78 Leung PY. et al. Inhibition of Factor XII-Mediated Activation of Factor XI Provides Protection Against Experimental Acute Ischaemic Stroke in Mice. Transl Stroke Res 2012; 3: 381-389.
79 Matafonov A. et al. Factor XII inhibition reduces thrombus formation in a primate thrombosis model. Blood 2014; 123: 1739-1746.
80 Larsson M. et al. A Factor XIIa Inhibitory Antibody Provides Thromboprotection in Extracorporeal Circulation Without Increasing Bleeding Risk. Sci Transl Med 2014; 6: 222ra17.
81 Revenko AS. et al. Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding. Blood 2011; 118: 5302-5311.
82 Yau JW. et al. Selective depletion of factor XI or factor XII with antisense oligo-nucleotides attenuates catheter thrombosis in rabbits. Blood 2014; 123: 2102-2107.
83 Bhattacharjee G. et al. Inhibition of vascular permeability by antisense-mediated inhibition of plasma kallikrein and coagulation factor 12. Nucleic Acid Ther 2013; 23: 175-187.
84 Back J. et al. Activated human platelets induce factor XIIa-mediated contact activation. Biochem Biophys Res Commun 2010; 391: 11-17.
85 Walsh PN, Griffin JH. Contributions of human platelets to the proteolytic activation of blood coagulation factors XII and XI. Blood 1981; 57: 106-118.
86 Walsh PN. The role of platelets in the contact phase of blood coagulation. Br J Haematol 1972; 22: 237-254.
87 Castaldi PA. et al. Availability of platelet Factor 3 and activation of factor XII in thrombasthenia. Nature 1965; 207: 422-424.
88 Van Der Meijden PE. et al. Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J Thromb Haemost 2012; 10: 1355-1362.
89 Kannemeier C. et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci USA 2007; 104: 6388-6393.
90 Smith SA. et al. Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci USA 2006; 103: 903-908.
91 Rao NN. et al. Inorganic polyphosphate: essential for growth and survival. Annu Rev Biochem 2009; 78: 605-647.
92 Choi SH. et al. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood 2011; 118: 6963-6970.
93 Semeraro F. et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood 2011; 118: 1952-1961.
94 Mutch NJ. et al. Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin. Blood 2010; 115: 3980-3988.
95 Smith SA. et al. Polyphosphate exerts differential effects on blood clotting, depending on polymer size. Blood 2010; 116: 4353-4359.
96 Ghosh S. et al. Inositol hexakisphosphate kinase 1 maintains haemostasis in mice by regulating platelet polyphosphate levels. Blood 2013; 122: 1478-1486.
97 Nickel KF. et al. Time-dependent degradation and tissue factor addition mask the ability of platelet polyphosphates in activating factor XII-mediated coagulation. Blood 2013; 122: 3847-3849.
98 Kulaev IS. et al. The Peculiarities of Polyphosphate Metabolism in Different Organism. In: Textbook of The Biochemistry of inorganic polyphosphate. 2nd ed.. John Wiley & Son; 2004. pp. 177-181.
99 Smith SA. et al. Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation. Blood 2012; 120: 5103-5110.
100 Bae JS. et al. Polyphosphate elicits pro-inflammatory responses that are counteracted by activated protein C in both cellular and animal models. J Thromb Haemost 2012; 10: 1145-1151.
101 Xu J. et al. Extracellular histones are major mediators of death in sepsis. Nat Med 2009; 15: 1318-1321.
102 Dinarvand P. et al. Polyphosphate amplifies proinflammatory responses of nuclear proteins through interaction with receptor for advanced glycation end products and P2Y1 purinergic receptor. Blood 2014; 123: 935-945.