Hamostaseologie 2012; 32(01): 51-55
DOI: 10.5482/ha-1187
Review
Schattauer GmbH

FSAP, a new player in inflammation?

FSAP, ein neuer Akteur bei Entzündungen?
F. Stephan
1   Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, Amsterdam, the Netherlands
,
L. A. Aarden
1   Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, Amsterdam, the Netherlands
,
S. Zeerleder
1   Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, Amsterdam, the Netherlands
2   Department of Haematology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
› Author Affiliations
Further Information

Publication History

received: 02 November 2011

accepted: 04 November 2011

Publication Date:
28 December 2017 (online)

Summary

Factor VII-activating protease (FSAP) is a serine protease in plasma that has a role in coagulation and fibrinolysis. FVII could be activated by purified FSAP in a tissue factor independent manner and pro-urokinase has been demonstrated to be a substrate for purified FSAP in-vitro. However, the physiological role of FSAP in haemostasis remains unclear. More recently FSAP is suggested to be involved in inflammation. It modulates vascular permeability directly and indirectly by the generation of bradykinin. Furthermore, FSAP is activated by dead cells induced by the inflammatory response and subsequently removes nucleosomes from apoptotic cells. FSAP activation can be detected in sepsis patients as well. However, whether FSAP activation upon inflammation is beneficial or detrimental remains an open question.

In this review the structure, activation mechanisms and the possible role of FSAP in inflammation are discussed.

Zusammenfassung

Die Faktor-VII-aktivierende Protease (FSAP) ist eine Serinprotease im Plasma, der eine Rolle bei Koagulation und Fibrinolyse zukommt. FVII konnte, unabhängig von Gewebefaktor, durch gereinigte FSAP aktiviert werden und es wurde gezeigt, dass Pro-Urokinase in vitro ein Substrat für gereinigte FSAP ist. Jedoch ist die physiologische Rolle von FSAP bei der Hämostase weiterhin unklar. Neuerdings wird eine Beteiligung von FSAP an Entzündungen vermutet. Durch die Bereitstellung von Bradykinin moduliert es direkt und indirekt die Gefäßpermeabilität. Darüber hinaus wird FSAP, induziert durch die entzündliche Reaktion, durch tote Zellen aktiviert und entfernt anschließend Nukleosomen aus apoptotischen Zellen. Die Aktivierung von FSAP kann bei septischen Patienten ebenfalls festgestellt werden. Es bleibt jedoch offen, ob die Aktivierung von FSAP bei einer Entzündung von Vorteil oder von Nachteil ist.

In dieser Übersicht werden Struktur, Aktivierungsmechanismus und die mögliche Rolle des FSAP bei Entzündungen diskutiert.

 
  • References

  • 1 Choi-Miura NH, Tobe T, Sumiya J. et al. Purification and characterization of a novel hyaluronan-binding protein (PHBP) from human plasma: it has three EGF, a kringle and a serine protease domain, similar to hepatocyte growth factor activator. J Biochem (Tokyo) 1996; 119: 1157-1165.
  • 2 Hunfeld A, Etscheid M, Konig H. et al. Detection of a novel plasma serine protease during purification of vitamin K-dependent coagulation factors. FEBS Lett 1999; 456: 290-294.
  • 3 Romisch J, Feussner A, Vermohlen S, Stohr HA. A protease isolated from human plasma activating factor VII independent of tissue factor. Blood Coagul Fibrinolysis 1999; 10: 471-479.
  • 4 Sumiya J, Asakawa S, Tobe T. et al. Isolation and characterization of the plasma hyaluronan-binding protein gene. J Biochem 1997; 122: 983-990.
  • 5 Etscheid M, Hunfeld A, Konig H. et al. Activation of proPHBSP, the zymogen of a plasma hyaluronan binding serine protease, by an intermolecular autocatalytic mechanism. Biol Chem 2000; 381: 1223-1231.
  • 6 Kannemeier C, Feussner A, Stohr HA. et al. Factor VII and single-chain plasminogen activator-activating protease: activation and autoactivation of the proenzyme. Eur J Biochem 2001; 268: 3789-3796.
  • 7 Roemisch J, Feussner A, Nerlich C. et al. The frequent Marburg I polymorphism impairs the prourokinase activating potency of the factor VII activating protease (FSAP). Blood Coagul Fibrinolysis 2002; 13: 433-441.
  • 8 Muhl L, Galuska SP, Oorni K. et al. High negative charge-to-size ratio in polyphosphates and heparin regulates factor VII-activating protease. FEBS J 2009; 276: 4828-4839.
  • 9 Altincicek B, Shibamiya A, Trusheim H. et al. A positively charged cluster in the epidermal growth factor-like domain of factor VII-activating protease (FSAP) is essential for polyanion binding. Biochem J 2006; 394: 687-692.
  • 10 Nakazawa F, Kannemeier C, Shibamiya A. et al. Extracellular RNA is a natural cofactor for the (auto-)activation of factor VII-activating protease (FSAP). Biochem J 2005; 385: 831-838.
  • 11 Yamamichi S, Nishitani M, Nishimura N. et al. Polyamine-promoted autoactivation of plasma hyaluronan-binding protein. J Thromb Haemost 2010; 08: 559-566.
  • 12 Stephan F, Hazelzet JA, Bulder I. et al. Activation of factor VII-activating protease in human inflammation. Crit Care 2011; 15: R110.
  • 13 Yamamichi S, Fujiwara Y, Kikuchi T. et al. Extracellular histone induces plasma hyaluronan-binding protein activation in vivo. Biochem Biophys Res Commun 2011; 409: 483-488.
  • 14 Choi-Miura NH, Saito K, Takahashi K. et al. Regulation mechanism of the serine protease activity of plasma hyaluronan binding protein. Biol Pharm Bull 2001; 24: 221-225.
  • 15 Romisch J, Vermohlen S, Feussner A, Stohr H. The FVII activating protease cleaves single-chain plasminogen activators. Haemostasis 1999; 29: 292-299.
  • 16 Wygrecka M, Morty RE, Markart P. et al. Plasminogen activator inhibitor-1 is an inhibitor of factor VII-activating protease in patients with acute respiratory distress syndrome. J Biol Chem 2007; 282: 21671-21682.
  • 17 Willeit J, Kiechl S, Weimer T. et al. Marburg I polymorphism of factor VII-activating protease. Circulation 2003; 107: 667-670.
  • 18 Ireland H, Miller GJ, Webb KE. et al. The factor VII activating protease G511E (Marburg) variant and cardiovascular risk. Thromb Haemost 2004; 92: 986-992.
  • 19 Kannemeier C, Al-Fakhri N, Preissner KT, Kanse SM. Factor VII-activating protease inhibits growth factor-mediated cell proliferation and migration of vascular smooth muscle cells. FASEB J 2004; 18: 728-730.
  • 20 Shibamiya A, Muhl L, Tannert-Otto S. et al. Nucleic acids potentiate factor VII-activating protease (FSAP)-mediated cleavage of platelet-derived growth factor-BB and inhibition of vascular smooth muscle cell proliferation. Biochem J 2007; 404: 45-50.
  • 21 Parahuleva MS, Kanse SM, Parviz B. et al. Factor seven activating protease (FSAP) expression in human monocytes and accumulation in unstable coronary atherosclerotic plaques. Atherosclerosis 2008; 196: 164-171.
  • 22 Sedding D, Daniel JM, Muhl L. et al. The G534E polymorphism of the gene encoding the factor VIIactivating protease is associated with cardiovascular risk due to increased neointima formation. J Exp Med 2006; 203: 2801-2807.
  • 23 Abraham E, Reinhart K, Opal S. et al. Efficacy and safety of tifacogin in severe sepsis: a randomized controlled trial. JAMA 2003; 290: 238-247.
  • 24 Bernard GR, Vincent JL, Laterre PF. et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709.
  • 25 Warren BL, Eid A, Singer P. et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis. JAMA 2001; 286: 1869-1878.
  • 26 Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest 2005; 128: 2864-2875.
  • 27 Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 2006; 06: 813-822.
  • 28 Papathanassoglou ED, Moynihan JA, Ackerman MH. Does programmed cell death play a role in the development of multiple organ dysfunction in critically ill patients?. Crit Care Med 2000; 28: 537-549.
  • 29 Zeerleder S, Zwart B, Wuillemin WA. et al. Elevated nucleosome levels in systemic inflammation and sepsis. Crit Care Med 2003; 31: 1947-1951.
  • 30 Van Till JW, van Veen SQ, den Broeder V. et al. Compartmental apoptosis and neutrophil accumulation in severe peritonitis. J Surg Res 2010; 164: 321-328.
  • 31 Massberg S, Grahl L, von Bruehl ML. et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 2010; 16: 887-896.
  • 32 Xu J, Zhang X, Pelayo R. et al. Extracellular histones are major mediators of death in sepsis. Nat Med 2009; 15: 1318-1321.
  • 33 Xu J, Zhang X, Monestier M. et al. Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. J Immunol 2011; 187: 2626-2631.
  • 34 Zeerleder S, Zwart B, Te VH. et al. A plasma nucleosome releasing factor (NRF) with serine protease activity is instrumental in removal of nucleosomes from secondary necrotic cells. FEBS Lett 2007; 581: 5382-5388.
  • 35 Zeerleder S, Zwart B, Te VH. et al. Nucleosome-releasing factor: a new role for factor VII-activating protease (FSAP). FASEB J 2008; 22: 4077-4084.
  • 36 Hack CE, Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 2001; 29 (Suppl. 07) S21-S27.
  • 37 Henrich M, Gruss M, Weigand MA. Sepsis-induced degradation of endothelial glycocalix. Scientific World Journal 2010; 10: 917-923.
  • 38 Kumar P, Shen Q, Pivetti CD. et al. Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Expert Rev Mol Med 2009; 11: e19.
  • 39 Etscheid M, Beer N, Kress JA. et al. Inhibition of bFGF/EGF-dependent endothelial cell proliferation by the hyaluronan-binding protease from human plasma. Eur J Cell Biol 2004; 82: 597-604.
  • 40 Etscheid M, Beer N, Fink E. et al. The hyaluronanbinding serine protease from human plasma cleaves HMW and LMW kininogen and releases bradykinin. Biol Chem 2002; 383: 1633-1643.
  • 41 Leeb-Lundberg LM. Bradykinin specificity and signaling at GPR100 and B2 kinin receptors. Br J Pharmacol 2004; 143: 931-932.
  • 42 Sharma JN, Al-Sherif GJ. Pharmacologic targets and prototype therapeutics in the kallikrein-kinin system. Sci World J 2006; 06: 1247-1261.
  • 43 Barratt-Due A, Johansen HT, Sokolov A. et al. The role of bradykinin and the effect of the bradykinin receptor antagonist icatibant in porcine sepsis. Shock 2011; 36: 517-523.
  • 44 Pixley RA, De La Cadena R, Page JD. et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. J Clin Invest 1993; 91: 61-68.
  • 45 Mambetsariev N, Mirzapoiazova T, Mambetsariev B. et al. Hyaluronic Acid binding protein 2 is a novel regulator of vascular integrity. Arterioscler Thromb Vasc Biol 2010; 30: 483-490.