Thrombomodulin and its role in inflammation

Seminars in Immunopathology

Volumn 34, Issue 1, 2012, Pages 107-125

  Conway, Edward M ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Arthritis; Atherosclerosis; C type lectin; Chondroitin sulfate; Coagulation; EGF; Endothelial; Innate immunity; Leukocyte; Protein C; TAFI

Indexed keywords

CALCIUM ION; COMPLEMENT; HEPARIN; HIGH MOBILITY GROUP B1 PROTEIN; LECTIN; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN C; PROTEIN KINASE C; RECOMBINANT THROMBOMODULIN; THROMBIN; THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR; THROMBOMODULIN; PLASMA PROTEIN; THBD PROTEIN, HUMAN;

AMINO TERMINAL SEQUENCE; ARTHRITIS; ASTHMA; ATHEROSCLEROSIS; BINDING AFFINITY; BINDING SITE; BLEEDING; BLOOD CLOTTING; CALCIUM BINDING; CARDIOVASCULAR RISK; CELL ADHESION; CELL PROLIFERATION; DISSEMINATED INTRAVASCULAR CLOTTING; DOWN REGULATION; DRUG MECHANISM; DRUG SAFETY; ENDOCYTOSIS; ENZYME ACTIVATION; HEART MUSCLE ISCHEMIA; HEAT STROKE; HOMEOSTASIS; HUMAN; IMMUNOMODULATION; IMMUNOREGULATION; INFECTION; INFLAMMATION; ISCHEMIA; LUNG INJURY; MUTATIONAL ANALYSIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REPERFUSION INJURY; RESTENOSIS; REVIEW; SPINAL CORD INJURY; STRUCTURE ANALYSIS; THROMBOSIS; TRANSCRIPTION REGULATION; UPREGULATION; ANIMAL; BLOOD; ENDOTHELIUM CELL; GENE EXPRESSION REGULATION; IMMUNOLOGY; METABOLISM; NEOPLASM;

ANIMALS; BLOOD PROTEINS; DISSEMINATED INTRAVASCULAR COAGULATION; ENDOTHELIAL CELLS; GENE EXPRESSION REGULATION; HUMANS; INFECTION; INFLAMMATION; NEOPLASMS; THROMBOMODULIN; THROMBOSIS;

EID: 84857860942     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-011-0282-8     Document Type: Review

References (275)

1. Owen WG, Esmon CT (1981) Functional proerties of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. J Biol Chem 256:5532-5535 (Pubitemid 11035389)
2. Esmon CT, Owen WG (2004) The discovery of thrombomodulin. J Thromb Haemost 2:209-213 (Pubitemid 40186031)
3. Ulutin ON, Seegers WH (1962) Autoprothrombin II and autoprothrombin II anticoagulant. Thromb Diath Haemorrh 7 (Suppl):256-263
4. Esmon CT, Stenflo J, Suttie JW (1976) A new vitamin K-dependent protein. A phospholipid-binding zymogen of a serine esterase. J Biol Chem 251:3052-3056
5. Stenflo J (1976) A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization. J Biol Chem 251:355-363
6. Kisiel W, Canfield WM, Ericsson EH, Davie EW (1977) Anticoagulant properties of bovine plasma protein C following activation of thrombin. Biochemistry 16:5824-5831 (Pubitemid 8255122)
7. Salem HH, Maruyama I, Ishii H, Majerus PW (1984) Isolation and characterization of thrombomodulin from human placenta. J Biol Chem 259:12246-12251 (Pubitemid 14019764)
8. Maruyama I, Bell C, Majerus P (1985) Thrombomodulin is found on endothelium of arteries, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol 101:363-371 (Pubitemid 15239110)
9. Kawanami O, Jin E, Ghazizadeh M, Fujiwara M, Jiang L, Nagashima M et al (2000) Heterogeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels. J Nippon Med Sch 67:118-125
10. Raife TJ, Lager DJ, Madison KC, Piette WW, Howard EJ, Sturm MT et al (1994) Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation. J Clin Invest 93:1846-1851
11. Conway E, Nowakowski B, Steiner-Mosonyi M (1992) Human neutrophils synthesize thrombomodulin that does not promote thrombin-dependent protein C activation. Blood 80:1254-1263
12. Conway E, Nowakowski B (1993) Biologically active thrombo-modulin is synthesized by adherent synovial fluid cells and is elevated in synovial fluid of patients with rheumatoid arthritis. Blood 81:726-733 (Pubitemid 23040865)
13. McCachren SS, Diggs J, Weinberg JB, Dittman WA (1991) Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages. Blood 78:3128-3132
14. Soff GA, Jackman RW, Rosenberg RD (1991) Expression of thrombomodulin by smooth muscle cells in culture: different effects of tumor necrosis factor and cyclic adenosine monophosphate on thrombomodulin expression by endothelial cells and smooth muscle cells in culture. Blood 77:515-518
15. Boffa M-C, Burke B, Haudenschild C (1987) Preservation of thrombomodulin antigen on vascular and extravascular surfaces. J Histochem Cytochem 35:1267-1276
16. Boffa M, Jackman R, Peyri N, Boffa J, George B (1991) Thrombomodulin in the central nervous system. Nouv Rev Fr Hematol 33:423-429
17. Maillard C, Berruyer M, Serre CM, Amiral J, Dechavanne M, Delmas PD (1993) Thrombomodulin is synthesized by osteoblasts, stimulated by 1,25-(OH)2D3 and activates protein C at their cell membrane. Endocrinology 133:668-674 (Pubitemid 23238878)
18. Imada M, Imada S, Iwasaki H, Kume A, Yamaguchi H, Moore E (1987) Fetomodulin: marker surface protein of fetal development which is modulatable by cyclic AMP. Dev Biol 122:483-491
19. Imada S, Yamaguchi H, Nagumo M, Katayanagi S, Iwasaki H, Imada M (1990) Identification of fetomodulin, a surface marker protein of fetal development, as thrombomodulin by gene cloning and functional assays. Dev Biol 140:113-122
20. Wong V, Hofman FM, Ishii H, Fisher M (1991) Regional distribution of thrombomodulin in human brain. Brain Res 556:1-5
21. Tran ND, Wang L, Schreiber SS, Zlokovic B, Fisher M (1998) Measurement of thrombomodulin mRNA expression in brain capillaries by polymerase chain reaction [in process citation]. Thromb Res 91:191-197 (Pubitemid 28429588)
22. Wang L, Tran N, Kittaka M, Fisher M, Schreiber S, Zlokovic B (1997) Thrombomodulin expression in bovine brain capillaries. Anticoagulant function of the blood-brain barrier, regional differences, and regulatory mechanisms. Arterioscler Thromb Vasc Biol 17:3139-3146 (Pubitemid 28016069)
23. Jackson MT, Smith MM, Smith SM, Jackson CJ, Xue M, Little CB (2009) Activation of cartilage matrix metalloproteinases by activated protein C. Arthritis Rheum 60:780-791
24. Wang L, Bastarache JA, Wickersham N, Fang X, Matthay MA, Ware LB (2007) Novel role of the human alveolar epithelium in regulating intra-alveolar coagulation. Am J Respir Cell Mol Biol 36:497-503 (Pubitemid 46623009)
25. Kawamura H, Hiramatsu Y, Watanabe I (1996) Localization of thrombomodulin in a rabbit eye. Curr Eye Res 15:938-942 (Pubitemid 26332232)
26. Yerkovich ST, Roponen M, Smith ME, McKenna K, Bosco A, Subrata LS, et al (2009) Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response. J Allergy Clin Immunol 123:209.e4-216.e4.
27. Isermann B, Hendrickson SB, Hutley K, Wing M, Weiler H (2001) Tissue-restricted expression of thrombomodulin in the placenta rescues thrombomodulin-deficient mice from early lethality and reveals a secondary developmental block. Development 128:827-838 (Pubitemid 32288194)
28. Isermann B, Sood R, Pawlinski R, Zogg M, Kalloway S, Degen JL et al (2003) The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Nat Med 9:331-337 (Pubitemid 36362789)
29. Boehme MW, Deng Y, Raeth U, Bierhaus A, Ziegler R, Stremmel W et al (1996) Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: in vivo and in vitro studies. Immunology 87:134-140 (Pubitemid 26027567)
30. Lohi O, Urban S, Freeman M (2004) Diverse substrate recognition mechanisms for rhomboids: thrombomodulin is cleaved by mammalian rhomboids. Curr Biol 14:236-241 (Pubitemid 38215352)
31. Yamamoto S, Mizoguchi T, Tamaki T, Ohkuchi M, Kimura S, Aoki N (1993) Urinary thrombomodulin, its isolation and characterization. J Biochem 113:433-440 (Pubitemid 23136039)
32. Jackman RW, Beeler DL, Fritze L, Soff G, Rosenberg RD (1987) Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control. Proc Natl Acad Sci USA 84:6425-6429 (Pubitemid 18002810)
33. Wen D, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE (1987) Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene. Biochemistry 6:2960-2967
34. Suzuki K, Kusomoto H, Deyashiki Y, Hishioka J, Maruyama I, Zushi M et al (1987) Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. EMBO J 6:1891-1897
35. Suzuki K, Deyashiki Y, Nishioka J, Kurachi K, Akira M, Yamamoto S et al (1987) Characterization of a cDNA for human protein C inhibitor. A new member of the plasma serine protease inhibitor superfamily. J Biol Chem 262:611-616 (Pubitemid 17005226)
36. Villoutreix B, Dahlback B (1998) Molecular model for the C-type lectin domain of human thrombomodulin. J Mol Model 4:310-322 (Pubitemid 128664731)
37. Lu R, Esmon NL, Esmon CT, Johnson AE (1989) The active site of the thrombin-thrombomodulin complex. J Biol Chem 264:12956-12962
38. Weisel JW, Nagaswami C, Young TA, Light DR (1996) The shape of thrombomodulin and interactions with thrombin as determined by electron microscopy. J Biol Chem 271: 31485-31490 (Pubitemid 26408605)
39. Hamada H, Ishii H, Sakyo K, Horie S, Nishiki K, Kazama M (1995) The epidermal growth factor-like domain of recombinant human thrombomodulin exhibits mitogenic activity for Swiss 3T3 cells. Blood 86:225-233
40. Tohda G, Oida K, Okada Y, Kosaka S, Okada E, Takahashi S et al (1998) Expression of thrombomodulin in atherosclerotic lesions and mitogenic activity of recombinant thrombomodulin in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 18:1861-1869 (Pubitemid 28565747)
41. Kurosawa S, Stearns DJ, Jackson KW, Esmon CT (1988) A 10- kDa cyanogen bromide fragment from the epidermal growth factor homology domain of rabbit thrombomodulin contains the primary thrombin binding site. J Biol Chem 263:5993-5996
42. Zushi M, Gomi K, Yamamoto S, Maruyama I, Hayashi T, Suzuki K (1989) The last three consecutive epidermal growth factor-like structures of human thrombomodulin comprise the minimum functional domain for protein C-activating cofactor activity and anticoagulant activity. J Biol Chem 264:10351-10353 (Pubitemid 19161593)
43. Suzuki K, Hayashi T, Nishioka J, Kosaka Y, Zushi M, Honda G et al (1989) A domain composed of epidermal growth factor-like structures of human thrombomodulin is essential for thrombin binding and for protein C activation. J Biol Chem 264:4872-4876 (Pubitemid 19092897)
44. Wang W, Nagashima M, Schneider M, Morser J, Nesheim M (2000) Elements of the primary structure of thrombomodulin required for efficient thrombin-activable fibrinolysis inhibitor activation. J Biol Chem 275:22942-22947 (Pubitemid 30646181)
45. Schenk-Braat EA, Morser J, Rijken DC (2001) Identification of the epidermal growth factor-like domains of thrombomodulin essential for the acceleration of thrombin-mediated inactivation of single-chain urokinase-type plasminogen activator. Eur J Biochem 268:5562-5569 (Pubitemid 34183321)
46. Bourin MC, Lundgren ÅE, Lindahl U (1990) Isolation and characterization of the glycosaminoglycan component of rabbit thrombomodulin proteoglycan. J Biol Chem 265:15424-15431
47. Conway E, Nowakowski B, Steiner-Mosonyi M (1994) Thrombomodulin lacking the cytoplasmic domain efficiently internalizes thrombin via nonclathrin-coated, pit-mediated endocytosis. J Cell Physiol 158:285-298 (Pubitemid 24063556)
48. Conway EM, Pollefeyt S, Cornelissen J, DeBaere I, Steiner- Mosonyi M, Weitz JI et al (1999) Structure-function analyses of thrombomodulin by gene-targeting in mice: the cytoplasmic domain is not required for normal fetal development. Blood 93:3442-3450 (Pubitemid 29220911)
49. Adler M, Seto MH, Nitecki DE, Lin JH, Light DR, Morser J (1995) The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin. J Biol Chem 270:23366-23372
50. Wood MJ, Sampoli Benitez BA, Komives EA (2000) Solution structure of the smallest cofactor-active fragment of thrombomodulin. Nat Struct Biol 7:200-204 (Pubitemid 30140764)
51. Fuentes-Prior P, Iwanaga Y, Huber R, Pagila R, Rumennik G, Seto M et al (2000) Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex [see comments]. Nature 404:518-525 (Pubitemid 30186897)
52. Koeppe JR, Seitova A, Mather T, Komives EA (2005) Thrombomodulin tightens the thrombin active site loops to promote protein C activation. Biochemistry 44:14784-14791 (Pubitemid 41612258)
53. Tsiang M, Lentz SR, Sadler JE (1992) Functional domains of membrane-bound human thrombomodulin. EGF-like domains four to six and the serine/threonine- rich domain are required for cofactor activity. J Biol Chem 267:6164-6170
54. Nesheim M, Wang W, Boffa M, Nagashima M, Morser J, Bajzar L (1997) Thrombin, thrombomodulin and TAFI in the molecularlink between coagulation and fibrinolysis. Thromb Haemost 78:386-391 (Pubitemid 27289272)
55. Wu C, Kim PY, Manuel R, Seto M, Whitlow M, Nagashima M, Morser J, Gils A, Declerck P, Nesheim ME (2009) The roles of selected arginine and lysine residues of TAFI (Pro-CPU) in its activation to TAFIa by the thrombin-thrombomodulin complex. J Biol Chem 284:7059-7067
56. Light DR, Glaser CB, Betts M, Blasko E, Campbell E, Clarke JH et al (1999) The interaction of thrombomodulin with Ca2+. Eur J Biochem 262:522-533
57. Adams TE, Huntington JA (2006) Thrombin-cofactor interactions: structural insights into regulatory mechanisms. Arterioscler Thromb Vasc Biol 26:1738-1745 (Pubitemid 44305326)
58. Grinnell BW, Berg DT (1996) Surface thrombomodulin modulates thrombin receptor responses on vascular smooth muscle cells. AmJ Physiol 270:H603-H609
59. Lafay M, Laguna R, Le Bonniec BF, Lasne D, Aiach M, Rendu F (1998) Thrombomodulin modulates the mitogenic response to thrombin of human umbilical vein endothelial cells. Thromb Haemost 79:848-852 (Pubitemid 28163866)
60. Esmon CT, Esmon NL, Harris KW (1982) Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation. J Biol Chem 257:7944-7947 (Pubitemid 13241217)
61. Esmon NL, Carroll RC, Esmon CT (1983) Thrombomodulin blocks the ability of thrombin to activate platelets. J Biol Chem 258:12238-12242 (Pubitemid 14230011)
62. Ye J, Esmon C, Johnson A (1993) The chondroitin sulfate moiety of thrombomodulin binds a second molecule of thrombin. J Biol Chem 268:2373-2379 (Pubitemid 23057854)
63. Stenflo J, Fernlund P (1982) Amino acid sequence of the heavy chain of bovine protein C. J Biol Chem 257:12180-12190
64. Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT (1996) The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA 93:10212-10216 (Pubitemid 26314601)
65. Fukudome K, Ye X, Tsuneyoshi N, Tokunaga O, Sugawara K, Mizokami H et al (1998) Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor. J Exp Med 187:1029-1035 (Pubitemid 28176403)
66. Laszik Z, Mitro A, Taylor FB Jr, Ferrell G, Esmon CT (1997) Human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway. Circulation 96:3633-3640 (Pubitemid 27513443)
67. Fukudome K, Esmon C (1995) Molecular cloning and expression of murine and bovine endothelial cell protein C/activated protein C receptor (EPCR). J Biol Chem 270:5571-5577
68. Dahlback B, Villoutreix BO (2005) Regulation of blood coagulation by the protein C anticoagulant pathway: novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol 25:1311-1320 (Pubitemid 40923345)
69. Slungaard A, Fernandez JA, Griffin JH, Key NS, Long JR, Piegors DJ et al (2003) Platelet factor 4 enhances generation of activated protein C in vitro and in vivo. Blood 102:146-151 (Pubitemid 36759648)
70. Slungaard A (2005) Platelet factor 4: a chemokine enigma. Int J Biochem Cell Biol 37:1162-1167
71. Cooper ST, Rezaie AR, Esmon CT, Church FC (2002) Inhibition of a thrombin anion-binding exosite-2 mutant by the glycosaminoglycan-dependent serpins protein C inhibitor and heparin cofactor II. Thromb Res 107:67-73 (Pubitemid 35284428)
72. Yang L, Manithody C, Walston TD, Cooper ST, Rezaie AR (2003) Thrombomodulin enhances the reactivity of thrombin with protein C inhibitor by providing both a binding site for the serpin and allosterically modulating the activity of thrombin. J Biol Chem 278:37465-37470 (Pubitemid 37175267)
73. Preissner KT, Delvos U, Muller-Berghaus G (1987) Binding of thrombin to thrombomodulin accelerates inhibition of the enzyme by antithrombin III. Evidence for a heparin-independent mechanism. Biochemistry 26:2521-2528 (Pubitemid 17081481)
74. Riewald M, Petrovan RJ, Donner A, Ruf W (2003) Activated protein C signals through the thrombin receptor PAR1 in endothelial cells. J Endotoxin Res 9:317-321 (Pubitemid 37193040)
75. Cheng T, Liu D, Griffin JH, Fernandez JA, Castellino F, Rosen ED et al (2003) Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med 9:338-342 (Pubitemid 36362790)
76. Krupiczojc MA, Scotton CJ, Chambers RC (2008) Coagulation signalling following tissue injury: focus on the role of factor Xa. Int J Biochem Cell Biol 40:1228-1237
77. Levi M (2010) The coagulant response in sepsis and inflammation. Hämostaseologie 30(10-12):14-16
78. Bajzar L, Manuel R, Nesheim M (1995) Purification and characterization of TAFI, a thrombin-activatable fibrinolysis inhibitor. J Biol Chem 270:14477-14484
79. Dai L, Mitchell M, Savidge G, Alhaq A (2004) The profibrinolytic effect of plasma thrombomodulin in factor XI deficiency and its implications in hemostasis. J Thromb Haemost 2:2200-2204 (Pubitemid 40185782)
80. Nagashima M, Yin ZF, Broze GJ Jr, Morser J (2002) Thrombin-activatable fibrinolysis inhibitor (TAFI) deficient mice. Front Biosci 7:d556-d568
81. Vercauteren E, Emmerechts J, Peeters M, Hoylaerts MF, Declerck PJ, Gils A (2011) Evaluation of the profibrinolytic properties of an anti-TAFI monoclonal antibody in a mouse thromboembolism model. Blood 117:4615-4622
82. Campbell WD, Lazoura E, Okada N, Okada H (2002) Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxy-peptidase N. Microbiol Immunol 46:131-134 (Pubitemid 34194973)
83. Myles T, Nishimura T, Yun TH, Nagashima M, Morser J, Patterson AJ, et al (2003) Thrombin activatable fibrinolysis inhibitor: a potential regulator of vascular inflammation. J Biol Chem 278:51059-51067 (Pubitemid 38020340)
84. Morser J, Gabazza EC, Myles T, Leung LL (2010) What has been learnt from the thrombin-activatable fibrinolysis inhibitor-deficient mouse? J Thromb Haemost 8:868-876
85. Kokame K, Zheng X, Sadler J (1998) Activation of thrombin-activatable fibrinolysis inhibitor requires epidermal growth factor-like domain 3 of thrombomodulin and is inhibited competitively by protein C. J Biol Chem 273: 12135-12139 (Pubitemid 28240575)
86. Glaser C, Morser J, Clarke J, Blasko E, McLean K, Kuhn I et al (1992) Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. J Clin Invest 90:2565-2573
87. Wood MJ, Becvar LA, Prieto JH, Melacini G, Komives EA (2003) NMR structures reveal how oxidation inactivates thrombomodulin. Biochemistry 42:11932-11942 (Pubitemid 37280643)
88. Wood MJ, Helena Prieto J, Komives EA (2005) Structural and functional consequences of methionine oxidation in thrombomodulin. Biochim Biophys Acta 1703:141-147 (Pubitemid 40170437)
89. Adams GN, Larusch GA, Stavrou E, Zhou Y, Nieman MT, Jacobs GH et al (2011) Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis. Blood 117:3929-3937
90. Mosnier LO (2011) Platelet factor 4 inhibits thrombomodulin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) by thrombin. J Biol Chem 286:502-510
91. DeMunk G, Groeneveld E, Rijken DC (1991) Acceleration of the thrombin inactivation of single chain urokinase-type plasminogen activator (Pro-urokinase) by thrombomodulin. J Clin Invest 88:1680-1684
92. Molinari A, Giorgetti C, Lansen J, Vaghi F, Orsini G, Faioni E et al (1992) Thrombomodulin is a cofactor for thrombin degradation of recombinant single-chain urokinase plasminogen activator "in vitro" and in a perfused rabbit heart model. Thromb Haemost 67:226-232
93. Amara U, Flierl MA, Rittirsch D, Klos A, Chen H, Acker B et al (2010) Molecular intercommunication between the complement and coagulation systems. J Immunol 185:5628-5636
94. Fu X, Parks WC, Heinecke JW (2008) Activation and silencing of matrix metalloproteinases. Semin Cell Dev Biol 19:2-13 (Pubitemid 350235984)
95. Moore KL, Esmon CT, Esmon NL (1989) Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. Blood 73:159-165 (Pubitemid 19040970)
96. Maruyama I, Majerus PW (1985) The turnover of thrombin-thrombomodulin complex in cultured human umbilical vein endothelial cells and A549 lung cancer cells. J Biol Chem 260:15432-15438 (Pubitemid 16170074)
97. Beretz A, Freysinnet J-M, Gauchy J, Schmitt DA, Klein-Soyer C, Edgell C-JS et al (1989) Stability of the thrombin-thrombomodulin complex on the surface of endothelial cells from human saphenous vein or from the cell line EA.hy 926. Biochem J 259:35-40 (Pubitemid 19100494)
98. Brisson C, Archipoff G, Harrmann M-L, Hanau D, Beretz A, Freyssinet J-M et al (1993) Antibodies to thrombomodulin induce receptor-mediated endocytosis in human saphenous vein endothelial cells. Thromb Haemost 68:737-743
99. Hirokawa K, Aoki N (1991) Regulatory mechanisms for thrombomodulin expression in human umbilical vein endothelial cells in vitro. J Cell Physiol 147:157-165 (Pubitemid 21910094)
100. Hirokawa K, Aoki N (1990) Up-regulation of thrombomodulin in human umbilical vein endothelial cells in vitro. J Biochem (Tokyo) 108:839-845
101. Maruyama I, Majerus P (1987) Protein C inhibits endocytosis of thrombin-thrombomodulin complexes in A549 lung cancer cells and human umbilical vein endothelial cells. Blood 69:1481-1484 (Pubitemid 17085311)
102. Conway E, Boffa M, Nowakowski B, Steiner-Mosonyi M (1992) An ultrastructural study of thrombomodulin endocytosis: internalization occurs via clathrin-coated and non-coated pits. J Cell Physiol 151:604-612
103. Tazawa T, Hirosawa S, Suzuki K, Hirokawa K, Aoki N (1993) Functional characterization of the 5′-regulatory region of the human thrombomodulin gene. J Biochem (Tokyo) 113:600-606 (Pubitemid 23166991)
104. Yu K, Morioka H, Fritze L, Beeler D, Jackman R, Rosenberg R (1992) Transcriptional regulation of the thrombomodulin gene. J Biol Chem 267:23237-23247
105. Niforas P, Sanderson G, Bird C, Bird P (1993) Characterization of the mouse thrombomodulin gene and functional analysis of the 5′ flanking region in F9 teratocarcinoma cells. Biochim Biophys Acta 1173:179-188 (Pubitemid 23162574)
106. Malek AM, Jackman R, Rosenberg RD, Izumo S (1994) Endothelial expression of thrombomodulin is reversibly regulated by fluid shear stress. Circ Res 74:852-860 (Pubitemid 24121588)
107. Ohji T, Urano H, Shirahata A, Yamagishi M, Higashi K, Gotoh S et al (1995) Transforming growth factor beta1 and beta2 induce down-modulation of thrombomodulin in human umbilical vein endothelial cells. Thromb Haemost 73:812-818
108. Ishii H, Tezuka T, Ishikawa H, Takada K, Oida K, Horie S (2003) Oxidized phospholipids in oxidized low-density lipoprotein down-regulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of RARbeta-RXRalpha heterodimers and Sp1 and Sp3 to their binding sequences in the TM promoter. Blood 101:4765-4774 (Pubitemid 36857733)
109. Rong Y, Zhang M, Zhang L, Wang XL, Shen YH (2010) JNK-ATF- 2 inhibits thrombomodulin (TM) expression by recruiting histone deacetylase4 (HDAC4) and forming a transcriptional repression complex in the TM promoter. FEBS Lett 584:852-858
110. Sandusky G, Berg DT, Richardson MA, Myers L, Grinnell BW (2002) Modulation of thrombomodulin-dependent activation of human protein C through differential expression of endothelial Smads. J Biol Chem 277:49815-49819 (Pubitemid 36014429)
111. Nan B, Yang H, Yan S, Lin PH, Lumsden AB, Yao Q et al (2005) C-reactive protein decreases expression of thrombomodulin and endothelial protein C receptor in human endothelial cells. Surgery 138:212-222 (Pubitemid 41253803)
112. Grey ST, Csizmadia V, Hancock WW (1998) Differential effect of tumor necrosis factor-alpha on thrombomodulin gene expression by human monocytoid (THP-1) cell versus endothelial cells [in process citation]. Int J Hematol 67:53-62 (Pubitemid 28167843)
113. Kim HK, Kim JE, Chung J, Kim YT, Kang SH, Han KS et al (2007) Lipopolysaccharide down-regulates the thrombomodulin expression of peripheral blood monocytes: effect of serum on thrombomodulin expression in the THP-1 monocytic cell line. Blood Coagul Fibrinol 18:157-164 (Pubitemid 46232837)
114. Conway EM, Rosenberg RD (1988) Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol Cell Biol 8:5588-5592
115. Starr ME, Ueda J, Takahashi H, Weiler H, Esmon CT, Evers BM et al (2010) Age-dependent vulnerability to endotoxemia is associated with reduction of anticoagulant factors activated protein C and thrombomodulin. Blood 115:4886-4893
116. Sohn RH, Deming CB, Johns DC, Champion HC, Bian C, Gardner K et al (2005) Regulation of endothelial thrombomodulin expression by inflammatory cytokines is mediated by activation of nuclear factor-kappa B. Blood 105:3910-3917 (Pubitemid 40656136)
117. Baeuerle PA (1998) IkappaB-NF-kappaB structures: at the interface of inflammation control. Cell 95:729-731
118. Hamaguchi E, Takamura T, Shimizu A, Nagai Y (2003) Tumor necrosis factor-alpha and troglitazone regulate plasminogen activator inhibitor type 1 production through extracellular signal-regulated kinase- and nuclear factor-kappaB-dependent pathways in cultured human umbilical vein endothelial cells. J Pharmacol Exp Ther 307:987-994 (Pubitemid 37494216)
119. Parry GC, Mackman N (1995) Transcriptional regulation of tissue factor expression in human endothelial cells. Arterioscler Thromb Vasc Biol 15:612-621
120. Conway EM, Carmeliet P (2004) The diversity of endothelial cells: a challenge for therapeutic angiogenesis. Genome Biol 5:207
121. Welch W (1993) Heat shock proteins functioning as molecular chaperones: their roles in normal and stressed cells. Phil Trans R Soc Lond 339:327-333
122. Morimoto R (1993) Cells in stress: transcriptional activation of heat shock genes. Science 259:1409-1410.
123. Udelsman R, Blake M, Stagg C, Li D, Putney D, Holbrook N (1993) Vascular heat shock protein expression in response to stress. J Clin Invest 91:465-473
124. Bielecka-Dabrowa A, Barylski M, Mikhailidis DP, Rysz J, Banach M (2009) HSP 70 and atherosclerosis - protector or activator? Expert Opin Ther Targets 13:307-317
125. Conway E, Liu L, Nowakowski B, Steiner-Mosonyi M, Jackman R (1994) Heat shock of vascular endothelial cells induces an upregulatory transcriptional response of the thrombomodulin gene that is delayed in onset and does not attenuate. J Biol Chem 269:22804-22810 (Pubitemid 24273394)
126. Drake T, Cheng J, Chang A, Taylor F (1993) Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Path 142:1458-1470 (Pubitemid 24058133)
127. Nawroth P, Stern D (1986) Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 163:740-745
128. Laszik Z, Carson CW, Nadasdy T, Johnson LD, Lerner MR, Brackett DJ et al (1994) Lack of suppressed renal thrombomodulin expression in a septic rat model with glomerular thrombotic microangiopathy. Lab Invest 70:862-867
129. Wong HR, Ryan M, Wispe JR (1997) Stress response decreases NF-kappaB nuclear translocation and increases I-kappaBalpha expression in A549 cells. J Clin Invest 99:2423-2428 (Pubitemid 27227720)
130. Calnek DS, Grinnell BW (1998) Thrombomodulin-dependent anticoagulant activity is regulated by vascular endothelial growth factor. Exp Cell Res 238:294-298 (Pubitemid 28366153)
131. Dittman WA, Kumada T, Majerus PW (1989) Transcription of thrombomodulin mRNA in mouse hemangioma cells is increased by cycloheximide and thrombin. Proc Natl Acad Sci USA 86:7179-7182 (Pubitemid 19240888)
132. Maruyama I, Soejima Y, Osame M, Ito T, Ogawa K, Yamamoto S et al (1991) Increased expression of thrombomodulin on the cultured human umbilical vein endothelial cells and mouse hemangioma cells by cyclic AMP. Thromb Res 61:301-310
133. Weiler GH, Yu K, Soff G, Gudas LJ, Rosenberg RD (1992) Thrombomodulin gene regulation by cAMP and retinoic acid in F9 embryonal carcinoma cells. Proc Natl Acad Sci USA 89:2155-2159
134. Shi J, Wang J, Zheng H, Ling W, Joseph J, Li D et al (2003) Statins increase thrombomodulin expression and function in human endothelial cells by a nitric oxide-dependent mechanism and counteract tumor necrosis factor alpha-induced thrombomodulin downregulation. Blood Coagul Fibrinol 14:575-585 (Pubitemid 37083174)
135. Rees DA, Giles P, Lewis MD, Ham J (2010) Adenosine regulates thrombomodulin and endothelial protein C receptor expression in folliculostellate cells of the pituitary gland. Purinergic Signal 6:19-29
136. Lentz SR, Sadler JE (1991) Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. J Clin Invest 88:1906-1914
137. Abe H, Okajima K, Okabe H, Takatsuki K, Binder BR (1994) Granulocyte proteases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro. J Lab Clin Med 123:874-881 (Pubitemid 2103605)
138. Redl H, Schlag G, Schiesser A, Davies J (1995) Thrombomodulin release in baboon sepsis: its dependence on the dose of Escherichia coli and the presence of tumor necrosis factor. J Infect Dis 171:1522-1527
139. Inomata M, Ishihara Y, Matsuyama T, Imamura T, Maruyama I, Noguchi T et al (2009) Degradation of vascular endothelial thrombomodulin by arginine- and lysine-specific cysteine proteases from Porphyromonas gingivalis. J Periodontol 80:1511-1517
140. Glusa E (1992) Vascular effects of thrombin. Sem Thromb Hemost 18:296-304
141. Bizios R, Lai L, Fenton JW 2nd, Malik AB (1986) Thrombin-induced chemotaxis and aggregation of neutrophils. J Cell Physiol 128:485-490
142. Kudhal K, Fisker S, Sonne O (1991) A thrombin receptor in resident rat peritoneal macrophages. Exp Cell Res 193:45-53 (Pubitemid 121004333)
143. Naldini A, Bernini C, Pucci A, Carraro F (2005) Thrombin-mediated IL-10 up-regulation involves protease-activated receptor (PAR)-1 expression in human mononuclear leukocytes. J Leukoc Biol 78:736-744 (Pubitemid 41292096)
144. Naldini A, Carney DH, Bocci V, Klimpel KD, Asuncion M, Soares LE et al (1993) Thrombin enhances T cell proliferative responses and cytokine production. Cell Immunol 147:367-377 (Pubitemid 23113934)
145. Naldini A, Carney DH, Pucci A, Carraro F (2002) Human alpha-thrombin stimulates proliferation of interferon-gamma differentiated, growth-arrested U937 cells, overcoming differentiation-related changes in expression of p21CIP1/ WAF1 and cyclin D1. J Cell Physiol 191:290-297 (Pubitemid 34462479)
146. Naldini A, Carney DH, Pucci A, Pasquali A, Carraro F (2000) Thrombin regulates the expression of proangiogenic cytokines via proteolytic activation of protease-activated receptor-1. Gen Pharmacol 35:255-259 (Pubitemid 34215118)
147. Naldini A, Pucci A, Carney DH, Fanetti G, Carraro F (2002) Thrombin enhancement of interleukin-1 expression in mononuclear cells: involvement of proteinase-activated receptor-1. Cytokine 20:191-199 (Pubitemid 37163471)
148. Chen L, Teng N, Buchanan J (1976) Mitogenicity of thrombin and surface alterations on mouse splenocytes. Exp Cell Res 101:41-46
149. Bar-Shavit R, Kahn AJ, Mann KG, Wilner GD (1986) Identification of a thrombin sequence with growth factor activity on macrophages. Proc Natl Acad Sci USA 83:976-980 (Pubitemid 16086396)
150. Bar-Shavit R, Hruska K, Kahn A, Wilner G (1986) Hormone-like activity of human thrombin. Ann NY Acad Sci 485:335-348 (Pubitemid 17022510)
151. Tatakis D, Dolce C, Dziak R (1989) Thrombin's effects on osteoblastic cells. I. Cytosolic calcium and phosphoinositides. Biochem Biophys Res Commun 164:119-127 (Pubitemid 19269704)
152. Furmaniak-Kazmierczak E, Cooke T, Manuel R, Scudamore A, Hoogendorn H, Giles A et al (1994) Studies of thrombin-induced proteoglycan release in the degradation of human and bovine cartilage. J Clin Invest 94:472-480 (Pubitemid 24250972)
153. Tang H, Low B, Rutherford SA, Hao Q (2005) Thrombin induces endocytosis of endoglin and type-II TGF-beta receptor and down-regulation of TGF-beta signaling in endothelial cells. Blood 105:1977-1985 (Pubitemid 40731781)
154. Vu TK, Hung DT, Wheaton VI, Coughlin SR (1991) Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64:1057-1068 (Pubitemid 121001193)
155. Woolkalis M, DeMelfi TJ, Blanchard N, Hoxie J, Brass L (1995) Regulation of thrombin receptors on human umbilical vein endothelial cells. J Biol Chem 270:9868-9875.
156. Minami T, Sugiyama A, Wu SQ, Abid R, Kodama T, Aird WC (2004) Thrombin and phenotypic modulation of the endothelium. Arterioscler Thromb Vasc Biol 24:41-53 (Pubitemid 38082410)
157. Coughlin SR, Camerer E (2003) PARticipation in inflammation. J Clin Invest 111:25-27 (Pubitemid 36134843)
158. Trejo J (2003) Protease-activated receptors: new concepts in regulation of G protein-coupled receptor signaling and trafficking. J Pharmacol Exp Ther 307:437-442
159. Steinhoff M, Buddenkotte J, Shpacovitch V, Rattenholl A, Moormann C, Vergnolle N et al (2005) Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev 26:1-43 (Pubitemid 40209385)
160. Bhattacharya A, Cohen ML (2000) Vascular contraction and relaxation to thrombin and trypsin: thrombomodulin preferentially attenuates thrombin-induced contraction. J Pharmacol Exp Ther 295:284-290
161. Olivot JM, Estebanell E, Lafay M, Brohard B, Aiach M, Rendu F (2001) Thrombomodulin prolongs thrombin-induced extracellular signal-regulated kinase phosphorylation and nuclear retention in endothelial cells. Circ Res 88:681-687 (Pubitemid 32378137)
162. Dufilho M, Millanvoye-Van Brussel E, Topal G, Walch L, Brunet A, Rendu F (2005) Endothelial thrombomodulin induces Ca2+ signals and no synthesis through epidermal growth factor receptor kinase and calmodulin kinase II. J Biol Chem 280:35999-36006 (Pubitemid 41633869)
163. Taylor FJ, Chang A, Esmon CT, Hinshaw LB (1991) Baboon model of Escherichia coli sepsis: description of its four stages and the role of tumor necrosis factor, tissue factors, and the protein C system in septic shock. Curr Stud Hematol Blood Transfus 58:8-14
164. Taylor F, Stearns-Kurosawa D, Kurosawa S, Ferrell G, Chang A, Laszik Z et al (2000) The endothelial cell protein C receptor aidsin host defense against Escherichia coli sepsis. Blood 95 (5):1680-1686 (Pubitemid 30120829)
165. Hancock WW, Sayegh MH, Sablinski T, Kut JP, Kupiec-Weglinski JW, Milford EL (1992) Blocking of mononuclear cell accumulation, cytokine production, and endothelial activation within rat cardiac allografts by CD4 monoclonal antibody therapy. Transplantation 53:1276-1280
166. Hirose K, Okajima K, Taoka Y, Uchiba M, Tagami H, Nakano K et al (2000) Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg 232:272-280 (Pubitemid 30616729)
167. Mizutani A, Okajima K, Uchiba M, Noguchi T (2000) Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation. Blood 95:3781-3787 (Pubitemid 30412850)
168. Levi M, Choi G, Schoots I, Schultz M, Van Der Poll T (2004) Beyond sepsis: activated protein C and ischemia-reperfusion injury. Crit Care Med 32:S309-312
169. Grey ST, Tsuchida A, Hau H, Orthner CL, Salem HH, Hancock WW (1994) Selective inhibitory effects of the anticoagulant activated protein C on the responses of human mononuclear phagocytes to LPS, IFN-gamma, or phorbol ester. J Immunol 153:3664-3672 (Pubitemid 24313871)
170. Brueckmann M, Hoffmann U, Dvortsak E, Lang S, Kaden JJ, Borggrefe M et al (2004) Drotrecogin alfa (activated) inhibits NF-kappa B activation and MIP-1-alpha release from isolated mononuclear cells of patients with severe sepsis. Inflamm Res 53:528-533 (Pubitemid 40110118)
171. Levi M, Dorffler-Melly J, Reitsma P, Buller H, Florquin S, van der Poll T et al (2003) Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C-deficient mice. Blood 101:4823-4827 (Pubitemid 36857741)
172. Ganopolsky JG, Castellino FJ (2004) A protein C deficiency exacerbates inflammatory and hypotensive responses in mice during polymicrobial sepsis in a cecal ligation and puncture model. Am J Pathol 165:1433-1446 (Pubitemid 39297747)
173. Weiler-Guettler H, Christie P, Beeler D, Healy A, Hancock W, Rayburn H et al (1998) A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state. J Clin Invest 101:1-9
174. Weiler H, Lindner V, Kerlin B, Isermann B, Hendrickson S, Cooley B et al (2001) Characterization of a mouse model for thrombomodulin deficiency. Arterioscler Thromb Vasc Biol 21:1531-1537 (Pubitemid 34219820)
175. Rijneveld AW, Weijer S, Florquin S, Esmon CT, Meijers JC, Speelman P, et al (2003) Thrombomodulin mutant mice with a strongly reduced capacity to generate activated protein C have an unaltered pulmonary immune response to respiratory pathogens and lipopolysaccharide. Blood 103:1702-1709 (Pubitemid 38268962)
176. Dahlback B (2003) The discovery of activated protein C resistance. J Thromb Haemost 1:3-9
177. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64-67 (Pubitemid 24144355)
178. Kerlin BA, Yan SB, Isermann BH, Brandt JT, Sood R, Basson BR et al (2003) Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia. Blood 102:3085-3092 (Pubitemid 37314741)
179. Weiler H, Kerlin B, Lytle MC (2004) Factor V Leiden polymorphism modifies sepsis outcome: evidence from animal studies. Crit Care Med 32:S233-238
180. Oganesyan V, Oganesyan N, Terzyan S, Qu D, Dauter Z, Esmon NL et al (2002) The crystal structure of the endothelial protein C receptor and a bound phospholipid. J Biol Chem 277:24851-24854 (Pubitemid 34951783)
181. Esmon CT (2004) Structure and functions of the endothelial cell protein C receptor. Crit Care Med 32:S298-S301
182. Kurosawa S, Stearns-Kurosawa DJ, Hidari N, Esmon CT (1997) Identification of functional endothelial protein C receptor in human plasma. J Clin Invest 100:411-418 (Pubitemid 27349089)
183. Kurosawa S, Stearns-Kurosawa DJ, Carson CW, D'Angelo A, Della Valle P, Esmon CT (1998) Plasma levels of endothelial cell protein C receptor are elevated in patients with sepsis and systemic lupus erythematosus: lack of correlation with thrombomodulin suggests involvement of different pathological processes. Blood 91:725-727 (Pubitemid 28053403)
184. Xu J, Qu D, Esmon NL, Esmon CT (2000) Metalloproteolytic release of endothelial cell protein C receptor. J Biol Chem 275:6038-6044 (Pubitemid 30115255)
185. Kurosawa S, Esmon CT, Stearns-Kurosawa DJ (2000) The soluble endothelial protein C receptor binds to activated neutrophils: involvement of proteinase-3 and CD11b/CD18. J Immunol 165:4697-4703
186. Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W (2002) Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 296:1880-1882. (Pubitemid 34596276)
187. Feistritzer C, Riewald M (2005) Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1- phosphate receptor-1 crossactivation. Blood 105:3178-3184
188. Ikeguchi H, Maruyama S, Morita Y, Fujita Y, Kato T, Natori Y et al (2002) Effects of human soluble thrombomodulin on experimental glomerulonephritis. Kidney Int 61:490-501 (Pubitemid 34102589)
189. Koyama T, Parkinson JF, Aoki N, Bang NU, Müller BG, Preissner KT (1991) Relationship between post-translational glycosylation and anticoagulant function of secretable recombinant mutants of human thrombomodulin. Br J Haematol 78:515-522
190. Bourin MC, Lindahl U (1990) Functional role of the polysaccharide component of rabbit thrombomodulin proteoglycan. Effects on inactivation of thrombin by antithrombin, cleavage of fibrinogen by thrombin and thrombin-catalysed activation of Factor V. Biochem J 270:419-425
191. Rabhi-Sabile S, Steiner-Mosonyi M, Pollefeyt S, Collen D, Pouvelle B, Gysin J et al (1999) Plasmodium falciparum-infected erythrocytes: a mutational analysis of cytoadherence via murine thrombomodulin. Thromb Haemost 81:815-821 (Pubitemid 29216571)
192. Warrell D, Molyneux M, Beales P (1990) Severe and complicated malaria. Trans R Soc Trop Med Hyg 84:1-65 (Pubitemid 20206697)
193. Rogerson SJ (2003) Sequestration: causes and consequences. Redox Rep 8:295-299
194. Gitau EN, Newton CR (2005) Review article: blood-brain barrier in falciparum malaria. Trop Med Int Health 10:285-292 (Pubitemid 40388976)
195. Fried M, Duffy P (1996) Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272:1502-1504. (Pubitemid 26200005)
196. Fried M, Duffy P (1998) Maternal malaria and parasite adhesion. J Mol Med 76:162-171 (Pubitemid 28098702)
197. Pouvelle B, Meyer P, Robert C, Bardel L, Gysin J (1997) Chondroitin-4-sulfate impairs in vitro and in vivo cytoadherence of Plasmodium falciparum infected erythrocytes. Mol Med 3:508-518 (Pubitemid 127499164)
198. Beeson JG, Chai W, Rogerson SJ, Lawson AM, Brown GV (1998) Inhibition of binding of malaria-infected erythrocytes by a tetradecasaccharide fraction from chondroitin sulfate A. Infect Immun 66:3397-3402 (Pubitemid 28303142)
199. Edano T, Kumai N, Mizoguchi T, Ohkuchi M (1998) The glycosylation sites and structural characteristics of oligosaccharides on recombinant human thrombomodulin. Int J Biochem Cell Biol 30:77-88 (Pubitemid 28189498)
200. Lin J-H, McLean K, Morser J, Young T, Wydro R, Andrews Wet al (1994) Modulation of glycosaminoglycan addition in naturallyexpressed and recombinant human thrombomodulin. J Biol Chem 269:25021-25030 (Pubitemid 24311770)
201. Gerlitz B, Hassell T, Vlahos CJ, Parkinson JF, Bang NU, Grinnell BW (1993) Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474. Biochem J 295:131-140 (Pubitemid 23298317)
202. Pouvelle B, Fusai T, Gysin J (1998) Revue generale. Plasmodium falciparum et chondroitin-4-sulfate: Le nouveau couple cle de al sequestration. Med Trop 58:187-198. (Pubitemid 33605345)
203. Pruna A, Peyri N, Berard M, Boffa M-C (1997) Thrombomodulin is synthesized by human mesangial cells. Kidney Int 51:687-693 (Pubitemid 27157952)
204. Salanti A, Dahlback M, Turner L, Nielsen MA, Barfod L, Magistrado P et al (2004) Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J Exp Med 200:1197-1203 (Pubitemid 39507059)
205. Dodd RB, Drickamer K (2001) Lectin-like proteins in model organisms: implications for evolution of carbohydrate-binding activity. Glycobiology 11:71R-79R (Pubitemid 32685209)
206. Vasta GR, Quesenberry M, Ahmed H, O'Leary N (1999) C-type lectins and galectins mediate innate and adaptive immune functions: their roles in the complement activation pathway. Dev Comp Immunol 23:401-420 (Pubitemid 29309616)
207. Drickamer K (1988) Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem 263:9557-9560
208. Sim RB, Tsiftsoglou SA (2004) Proteases of the complement system. Biochem Soc Trans 32:21-27 (Pubitemid 38283006)
209. Petersen T (1988) The amino-terminal domain of thrombomodulin and pancreatic stone protein are homologous with lectins. FEBS Lett 231:51-53
210. Patthy L (1988) Detecting distant homologies of mosaic proteins. Analysis of the sequences of thrombomodulin, thrombospondin, complement components C9, C8 alpha and C8 beta, vitronectin and plasma cell membrane glycoprotein PC-1. J Mol Biol 202:689-696
211. Opavsky R, Haviernik P, Jurkovicova D, Garin MT, Copeland NG, Gilbert DJ et al (2001) Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo. J Biol Chem 276:38795-38807
212. MacFadyen JR, Haworth O, Roberston D, Hardie D, Webster MT, Morris HR et al (2005) Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium. FEBS Lett 579:2569-2575 (Pubitemid 40615660)
213. McGreal E, Gasque P (2002) Structure-function studies of the receptors for complement C1q. Biochem Soc Trans 30:1010-1014 (Pubitemid 36002397)
214. Greenlee MC, Sullivan SA, Bohlson SS (2008) CD93 and related family members: their role in innate immunity. Curr Drug Targets 9:130-138 (Pubitemid 351461011)
215. Conway EM, Van de Wouwer M, Pollefeyt S, Jurk K, Van Aken H, De Vriese A et al (2002) The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways. J Exp Med 196:565-577 (Pubitemid 35024436)
216. Geudens N, Van de Wouwer M, Vanaudenaerde BM, Vos R, Van De Wauwer C, Verleden GM et al (2008) The lectin-like domain of thrombomodulin protects against ischaemia-reperfusion lung injury. Eur Respir J 32:862-870
217. Van de Wouwer M, Plaisance S, DeVries A, Waelkens E, Collen D, Persson J et al (2006) The lectin-like domain of thrombomodulin interferes with complement activation and protects against arthritis. J Thromb Haemost 4:1813-1824 (Pubitemid 44144810)
218. Abeyama K, Stern DM, Ito Y, Kawahara KI, Yoshimoto Y, Tanaka M, et al (2005) The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism. J Clin Invest 115:1267-1274 (Pubitemid 40629045)
219. Alleva LM, Yang H, Tracey KJ, Clark IA (2005) High mobility group box 1 (HMGB1) protein: possible amplification signal in the pathogenesis of falciparum malaria. Trans R Soc Trop Med Hyg 99:171-174 (Pubitemid 40104015)
220. Chen G, Li J, Qiang X, Czura CJ, Ochani M, Ochani K et al (2005) Suppression of HMGB1 release by stearoyl lysophosphatidylcholine: an additional mechanism for its therapeutic effects in experimental sepsis. J Lipid Res 46:623-627 (Pubitemid 43073271)
221. Yang H, Wang H, Czura CJ, Tracey KJ (2005) The cytokine activity of HMGB1. J Leukoc Biol 78:1-8 (Pubitemid 40979937)
222. Mun-Bryce S, Rosenberg G (1998) Matrix metalloproteinases in cerebrovascular disease. J Cereb Blood Flow Metab 18:1163-1172 (Pubitemid 28509829)
223. Schmidt AM, Yan SD, Yan SF, Stern DM (2000) The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta 1498:99-111
224. Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5:331-342 (Pubitemid 40516158)
225. Ito T, Kawahara K, Okamoto K, Yamada S, Yasuda M, Imaizumi H et al (2008) Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes. Arterioscler Thromb Vasc Biol 28:1825-1830
226. Esmon C (2005) Do-all receptor takes on coagulation, inflammation. Nat Med 11:475-477
227. Huang HC, Shi GY, Jiang SJ, Shi CS, Wu CM, Yang HY, et al (2003) Thrombomodulin-mediated cell adhesion: involvement of its lectin-like domain. J Biol Chem 278:46750-46759
228. Shi CS, Shi GY, Hsiao SM, Kao YC, Kuo KL, Ma CYet al (2008) Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response. Blood 112:3661-3670
229. Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G et al (2009) Thrombomodulin mutations in atypical hemolytic-uremic syndrome. New Engl J Med 361:345-357
230. Busso N, Morard C, Salvi R, Peclat V, So A (2003) Role of the tissue factor pathway in synovial inflammation. Arthritis Rheum 48:651-659 (Pubitemid 36302000)
231. Nakano S, Ikata T, Kinoshita I, Kanematsu J, Yasuoka S (1999) Characteristics of the protease activity in synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Clin Exp Rheumatol 17:161-170 (Pubitemid 29195820)
232. Yang YH, Hall P, Little CB, Fosang AJ, Milenkovski G, Santos L et al (2005) Reduction of arthritis severity in protease-activated receptor-deficient mice. Arthritis Rheum 52:1325-1332 (Pubitemid 40530144)
233. Li J, Ny A, Leonardsson G, Nandakumar KS, Holmdahl R, Ny T (2005) The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis. Am J Pathol 166:783-792 (Pubitemid 40315635)
234. Judex MO, Mueller BM (2005) Plasminogen activation/plasmin in rheumatoid arthritis: matrix degradation and more. Am J Pathol 166:645-647 (Pubitemid 40315621)
235. So AK, Varisco PA, Kemkes-Matthes B, Herkenne-Morard C, Chobaz-Peclat V, Gerster JC et al (2003) Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways. J Thromb Haemost 1:2510-2515
236. Pekovich SR, Bock PE, Hoover RL (2001) Thrombin-thrombomodulin activation of protein C facilitates the activation of progelatinase A. FEBS Lett 494:129-132 (Pubitemid 32289386)
237. Buisson-Legendre N, Smith S, March L, Jackson C (2004) Elevation of activated protein C in synovial joints in rheumatoidarthritis and its correlation with matrix metalloproteinase 2. Arthritis Rheum 50:2151-2156 (Pubitemid 38924392)
238. Laszik ZG, Zhou XJ, Ferrell GL, Silva FG, Esmon CT (2001) Down-regulation of endothelial expression of endothelial cell protein C receptor and thrombomodulin in coronary atherosclerosis. Am J Pathol 159:797-802 (Pubitemid 32847169)
239. Mathew M, Tay E, Cusi K (2010) Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects. Cardiovasc Diabetol 9:9
240. Soskic SS, Dobutovic BD, Sudar EM, Obradovic MM, Nikolic DM, Zaric BL, et al (2011) The peroxisome proliferator-activated receptors and atherosclerosis. Angiology [Epub ahead of print]
241. Mangan S, Clancy P, Golledge J (2008) Modulation of endothelial cell thrombomodulin by PPAR ligands - variation according to environment. Thromb Res 121:827-834 (Pubitemid 351491284)
242. Reriani MK, Dunlay SM, Gupta B, West CP, Rihal CS, Lerman LO, et al. Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil. 2011.
243. Lin SJ, Hsieh FY, Chen YH, Lin CC, Kuan II, Wang SH et al (2009) Atorvastatin induces thrombomodulin expression in the aorta of cholesterol-fed rabbits and in TNFalpha-treated human aortic endothelial cells. Histol Histopathol 24:1147-1159
244. Rossi J, Rouleau L, Tardif JC, Leask RL (2010) Effect of simvastatin on Kruppel-like factor2, endothelial nitric oxide synthase and thrombomodulin expression in endothelial cells under shear stress. Life Sci 87:92-99
245. Masamura K, Oida K, Kanehara H, Suzuki J, Horie S, Ishii H et al (2003) Pitavastatin-induced thrombomodulin expression by endothelial cells acts via inhibition of small G proteins of the Rho family. Arterioscler Thromb Vasc Biol 23:512-517 (Pubitemid 36337231)
246. Manthey HD, Thomas AC, Shiels IA, Zernecke A, Woodruff TM, Rolfe B, et al (2011) Complement C5a inhibition reduces atherosclerosis in ApoE-/- mice. FASEB J 25:2447-2455
247. Speidl WS, Kastl SP, Huber K, Wojta J (2011) Complement in atherosclerosis: friend or foe? J Thromb Haemost 9:428-440
248. Yamaji K, Wang Y, Liu Y, Abeyama K, Hashiguchi T, Uchimura T et al (2005) Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation. Thromb Res 115:319-325
249. Zorio E, Navarro S, Medina P, Estelles A, Osa A, Rueda J et al (2006) Circulating activated protein C is reduced in young survivors of myocardial infarction and inversely correlates with the severity of coronary lesions. J Thromb Haemost 4:1530-1536
250. Boffa MC, Karmochkine M (1998) Thrombomodulin: an overview and potential implications in vascular disorders. Lupus 7:S120-125
251. Lin SM, Wang YM, Lin HC, Lee KY, Huang CD, Liu CY et al (2008) Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis. Crit Care Med 36:683-689
252. Matondo Maya DW, Mewono L, Nkoma AM, Issifou S, Mavoungou E (2008) Markers of vascular endothelial cell damage and P. falciparum malaria: association between levels of both sE-selectin and thrombomodulin, and cytokines, hemoglobin and clinical presentation. Eur Cytokine Netw 19:123-130
253. Salomaa V, Matei C, Aleksic N, Sansores-Garcia L, Folsom AR, Juneja H et al (1999) Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: a case-cohort study. Lancet 353:1729-1734 (Pubitemid 29240370)
254. Wu KK (2003) Soluble thrombomodulin and coronary heart disease. Curr Opin Lipidol 14:373-375
255. Wu KK, Aleksic N, Ballantyne CM, Ahn C, Juneja H, Boerwinkle E (2003) Interaction between soluble thrombomodulin and intercellular adhesion molecule-1 in predicting risk of coronary heart disease. Circulation 107:1729-1732 (Pubitemid 36418351)
256. Ohlin A-K, Marlar R (1995) The first mutation identified in the thrombomodulin gene in a 45 year old man presenting with thromboembolic disease. Blood 85:330-336
257. Kunz G, Ohlin AK, Adami A, Zoller B, Svensson P, Lane DA (2002) Naturally occurring mutations in the thrombomodulin gene leading to impaired expression and function. Blood 99:3646-3653 (Pubitemid 34534534)
258. Konstantoulas CJ, Cooper J, Warnock G, Miller GJ, Humphries SE, Ireland H (2004) A combination of two common thrombomodulin gene variants (-1208-1209TTdelTT and A455V) influence risk of coronary heart disease: a prospective study in men. Atherosclerosis 177:97-104 (Pubitemid 39361143)
259. Doggen CJ, Kunz G, Rosendaal FR, Lane DA, Vos HL, Stubbs PJ et al (1998) A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men. Thromb Haemost 80:743-748 (Pubitemid 28521716)
260. Waugh JM, Yuksel E, Li J, Kuo MD, Kattash M, Saxena R et al (1999) Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbitmodel. Circ Res 84:84-92 (Pubitemid 29074883)
261. Mohri M, Oka M, Aoki Y, Gonda Y, Hirata S, Gomi K et al (1994) Intravenous extended infusion of recombinant human soluble thrombomodulin prevented tissue factor-induced disseminated intravascular coagulation in rats. Am J Hematol 45:298-303 (Pubitemid 24109905)
262. Gonda Y, Hirata S, Saitoh K, Aoki Y, Mohri M, Gomi K et al (1993) Antithrombotic effect of recombinant human soluble thrombomodulin on endotoxin-induced disseminated intravascular coagulation in rats. Thromb Res 71:325-335 (Pubitemid 23222875)
263. Uchiba M, Okajima K, Murakami K, Nawa K, Okabe H, Takatsuki K (1995) Recombinant human soluble thrombomodulin reduces endotoxin-induced pulmonary vascular injury via protein C activation in rats. Thromb Haemost 74:1265-1270
264. Iba T, Nakarai E, Takayama T, Nakajima K, Sasaoka T, Ohno Y (2009) Combination effect of antithrombin and recombinant human soluble thrombomodulin in a lipopolysaccharide induced rat sepsis model. Crit Care 13:R203.
265. Taoka Y, Okajima K, Uchiba M, Johno M (2000) Neuro-protection by recombinant thrombomodulin. Thromb Haemost 83:462-468
266. Kaneko H, Joubara N, Yoshino M, Yamazaki K, Mitumaru A, Miki Y et al (2000) Protective effect of human urinary thrombomodulin on ischemia-reperfusion injury in the canine liver. Eur Surg Res 32:87-93 (Pubitemid 30251766)
267. Ozaki T, Anas C, Maruyama S, Yamamoto T, Yasuda K, Morita Y et al (2008) Intrarenal administration of recombinant human soluble thrombomodulin ameliorates ischaemic acute renal failure. Nephrol Dial Transplant 23:110-119 (Pubitemid 351767375)
268. Sharfuddin AA, Sandoval RM, Berg DT, McDougal GE, Campos SB, Phillips CL et al (2009) Soluble thrombomodulin protects ischemic kidneys. J Am Soc Nephrol 20:524-534
269. Hagiwara S, Iwasaka H, Goto K, Ochi Y, Mizunaga S, Saikawa T, et al (2010) Recombinant thrombomodulin prevents heat stroke by inhibition of high mobility group box 1 protein in sera of rats. Shock 34:402-406
270. Sperling C, Salchert K, Streller U, Werner C (2004) Covalently immobilized thrombomodulin inhibits coagulation and complement activation of artificial surfaces in vitro. Biomaterials 25:5101-5113 (Pubitemid 38510396)
271. Moll S, Lindley C, Pescatore S, Morrison D, Tsuruta K, Mohri M et al (2004) Phase I study of a novel recombinant human soluble thrombomodulin, ART-123. J Thromb Haemost 2:1745-1751 (Pubitemid 40192715)
272. Kearon C, Comp P, Douketis J, Royds R, Yamada K, Gent M (2005) Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost 3:962-968 (Pubitemid 41632827)
273. Saito H, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Ohno R et al (2007) Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 5:31-41 (Pubitemid 44921064)
274. Levi M (2010) Japanese consensus for disseminated intravascular coagulation (DIC): is it a small world after all? Thromb Res 125:4-5
275. Takagi T, Taguchi O, Toda M, Ruiz DB, Bernabe PG, D'Alessandro-Gabazza CN, et al (2011) Inhibition of allergic bronchial asthma by thrombomodulin is mediated by dendritic cells. Am J Respir Crit Care Med 183:31-42