Thrombosis and Haemostasis, Table of Contents Thromb Haemost 2008; 99(01): 44-51DOI: 10.1160/TH07-08-0495 Blood Coagulation, Fibrinolysis and Cellular Haemostasis Schattauer GmbH Cathepsin G, a leukocyte protease, activates coagulation factor VIII Authors Author Affiliations Andrew J Gale 1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA Diana Rozenshteyn 1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA Recommend Article Abstract Full Text PDF Download(opens in new window) Keywords KeywordsFactor VIII - cathepsin G - thrombosis - inflammation - neutrophils References References 1 Gillis S, Furie BC, Furie B. Interactions of neutrophils and coagulation proteins. Semin Hematol 1997; 34: 336-342. 2 Travis J. Structure, function, and control of neutrophil proteinases. Am J Med 1988; 84: 37-42. 3 Allen DH, Tracy PB. Human coagulation factor is activated to the functional cofactor by elastase and cathepsin G expressed at the monocyte surface. J Biol Chem 1995; 270: 1408-1415. 4 Owen CA, Campbell MA, Sannes PL. et al. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism which neutrophils focus and preserve catalytic activity of serine proteinases. J Cell Biol 1995; 131: 775-789. 5 Sambrano GR, Huang W, Faruqi T. et al. Cathepsin G activates protease-activated receptor-4 in human platelets. J Biol Chem 2000; 275: 6819-6823. 6 Goel MS, Diamond SL. Neutrophil cathepsin promotes prothrombinase and fibrin formation under flow conditions by activating fibrinogen-adherent platelets. J Biol Chem 2003; 278: 9458-9463. 7 Bagoly Z, Haramura G, Muszbek L. Down-regulation of activated factor XIII by polymorphonuclear granulocyte proteases within fibrin clot. Thromb Haemost 2007; 98: 359-367. 8 Vehar GA, Davie EW. Preparation and properties of bovine factor VIII. Biochemistry 1980; 19: 401-410. 9 Eaton D, Rodriquez H, Vehar GA. Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity. Biochemistry 1986; 25: 505-512. 10 Lollar P, Knutson GJ, Fass DN. Activation of porcine factor VIII:C by thrombin and factor Xa. Biochemistry 1985; 24: 8056-8064. 11 Lollar P, Parker CG. Subunit structure of thrombinactivated porcine factor VIII. Biochemistry 1989; 28: 666-674. 12 Fay PJ, Haidaris PJ, Smudzin TM. Human factor VIIIa subunit structure. Reconstruction of factor VIIIa from the isolated A1/A3-C1-C2 dimer and A2 subunit. J Biol Chem 1991; 266: 8957-8962. 13 Lollar P, Parker ET, Fay PJ. Coagulant properties of hybrid human/porcine factor VIII molecules. J Biol Chem 1992; 267: 23652-23657. 14 Pipe SW, Eickhorst AN, McKinley SH. et al. Mild hemophilia A caused by increased rate of factor VIII A2 subunit dissociation: evidence for nonproteolytic inactivation of factor VIIIa in vivo. Blood 1999; 93: 176-183. 15 Samis JA, Garrett M, Manuel RP. et al. Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V. Blood 1997; 90: 1065-1074. 16 Camire RM, Kalafatis M, Tracy PB. Proteolysis of factor V by cathepsin G and elastase indicates that cleavage at Arg1545 optimizes cofactor function by facilitating factor Xa binding. Biochemistry 1998; 37: 11896-11906. 17 Plescia J, Altieri DC. Activation of Mac-1 (CD11b/CD18)-bound factor X by released cathepsin G defines an alternative pathway of leucocyte initiation of coagulation. Biochem J 1996; 319 ( Pt 3): 873-879. 18 McGee MP, Li LC. Functional difference between intrinsic and extrinsic coagulation pathways. Kinetics of factor X activation on human monocytes and alveolar macrophages. J Biol Chem 1991; 266: 8079-8085. 19 Bouchard BA, Tracy PB. The participation of leukocytes in coagulant reactions. J Thromb Haemost 2003; 1: 464-469. 20 Egbring R, Havemann K. Possible role of polymorphonuclear granulocyte proteases in blood coagulation. Havemann K, Janoff AS. editors. Neutral proteases of human polymorphonuclear leukocytes.. Baltimore-Munich: Urban & Schwarzenberg, Inc.; 1978: 442-458. 21 Kopec M, Bykowska K, Lopaciuk S. et al. Effects of neutral proteases from human leukocytes on structure and biological properties of human factor VIII. Thromb Haemost 1980; 43: 211-217. 22 Varadi K, Marossy K, Asboth G. et al. Inactivation of human Factor VIII by granulocyte proteases. Thromb Haemost 1980; 43: 45-48. 23 Fay PJ. Activation of factor VIII and mechanisms of cofactor action. Blood Rev 2004; 18: 1-15. 24 Gale AJ, Radtke KP, Cunningham MA. et al. Intrinsic stability and functional properties of disulfide bond-stabilized coagulation factor VIIIa variants. J Thromb Haemost 2006; 4: 1315-1322. 25 Gale AJ, Pellequer JL. An engineered interdomain disulfide bond stabilizes human blood coagulation factor VIIIa. J Thromb Haemost 2003; 1: 1966-1971. 26 Mesters RM, Houghten RA, Griffin JH. Identification of a sequence of human activated protein C (residues 390–404) essential for its anticoagulant activity. J Biol Chem 1991; 266: 24514-24519. 27 Hill-Eubanks DC, Parker CG, Lollar P. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin. Proc Natl Acad Sci USA 1989; 86: 6508-6512. 28 Polanowska J, Krokoszynska I, Czapinska H. et al. Specificity of human cathepsin G. Biochim Biophys Acta 1998; 1386: 189-198. 29 Regan LM, Fay PJ. Cleavage of factor VIII light chain is required for maximal generation of factor VIIIa activity. J Biol Chem 1995; 270: 8546-8552. 30 Fay PJ, Mastri M, Koszelak ME. et al. Cleavage of factor VIII heavy chain is required for the functional interaction of a2 subunit with factor IXA. J Biol Chem 2001; 276: 12434-12439. 31 Koszelak Rosenblum ME, Schmidt K, Freas J. et al. Cofactor activities of factor VIIIa and A2 subunit following cleavage of A1 subunit at Arg336. J Biol Chem 2002; 277: 11664-11669. 32 Nogami K, Wakabayashi H, Schmidt K. et al. Altered interactions between the A1 and A2 subunits of factor VIIIa following cleavage of A1 subunit by factor Xa. J Biol Chem 2003; 278: 1634-1641. 33 Nogami K, Wakabayashi H, Fay PJ. Mechanisms of factor Xa-catalyzed cleavage of the factor VIIIa A1 subunit resulting in cofactor inactivation. J Biol Chem 2003; 278: 16502-16509. 34 Parker ET, Pohl J, Blackburn MN. et al. Subunit structure and function of porcine factor Xa-activated factor VIII. Biochemistry 1997; 36: 9365-9373. 35 Owen CA, Campbell EJ. The cell biology of leukocyte- mediated proteolysis. J Leukoc Biol 1999; 65: 137-150. 36 Campbell EJ, Owen CA. The sulfate groups of chondroitin sulfate- and heparan sulfate-containing proteoglycans in neutrophil plasma membranes are novel binding sites for human leukocyte elastase and cathepsin G. J Biol Chem 2007; 282: 14645-14654.