The role of thrombomodulin lectin-like domain in inflammation

Journal of Biomedical Science

Hua-Lin Wu²  Guey-Yueh Shi³  Cheng-Hsiang Kuo³  Yi-Heng Li¹ 

[1] Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan;Center for Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan;Department of Biochemistry and Molecular Biology, National Cheng Kung University, College of Medicine, Tainan 701, Taiwan

关键词: Inflammation;    Lectin;    Thrombomodulin;   

Others  :  825389
DOI  :  10.1186/1423-0127-19-34

 received in 2012-02-15, accepted in 2012-03-27,  发布年份 2012

【 摘 要 】

Thrombomodulin (TM) is a cell surface glycoprotein which is widely expressed in a variety of cell types. It is a cofactor for thrombin binding that mediates protein C activation and inhibits thrombin activity. In addition to its anticoagulant activity, recent evidence has revealed that TM, especially its lectin-like domain, has potent anti-inflammatory function through a variety of molecular mechanisms. The lectin-like domain of TM plays an important role in suppressing inflammation independent of the TM anticoagulant activity. This article makes an extensive review of the role of TM in inflammation. The molecular targets of TM lectin-like domain have also been elucidated. Recombinant TM protein, especially the TM lectin-like domain may play a promising role in the management of sepsis, glomerulonephritis and arthritis. These data demonstrated the potential therapeutic role of TM in the treatment of inflammatory diseases.

【 授权许可】

   
2012 Li et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE: Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene. Biochemistry 1987, 26:4350-4357.
• [2]Suzuki K, Kusumoto H, Deyashiki Y, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S: Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. EMBO J 1987, 6:1891-1897.
• [3]Esmon CT: The regulation of natural anticoagulant pathways. Science 1987, 235:1348-1352.
• [4]Esmon CT: The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989, 264:4743-4746.
• [5]Weiler H, Isermann B: Thrombomodulin. J Thromb Haemost 2003, 1:1515-1524.
• [6]Isermann B, Hendrickson SB, Zogg M, Wing M, Cummiskey M, Kisanuki YY, Yanagisawa M, Weiler H: Endothelium-specific loss of murine thrombomodulin disrupts the protein C anticoagulant pathway and causes juvenile-onset thrombosis. J Clin Invest 2001, 108:537-546.
• [7]Tohda G, Oida K, Okada Y, Kosaka S, Okada E, Takahashi S, Ishii H, Miyamori I: Expression of thrombomodulin in atherosclerotic lesions and mitogenic activity of recombinant thrombomodulin in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1998, 18:1861-1869.
• [8]Suzuki K, Nishioka J, Hayashi T, Kosaka Y: Functionally active thrombomodulin is present in human platelets. J Biochem 1988, 104:628-632.
• [9]McCachren SS, Diggs J, Weinberg JB, Dittman WA: Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages. Blood 1991, 78:3128-3132.
• [10]Li YH, Chung HC, Luo CY, Chao TH, Shyu KG, Shi GY, Wu HL: Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction. J Card Fail 2010, 16:980-990.
• [11]Zhang Y, Weiler-Guettler H, Chen J, Wilhelm O, Deng Y, Qiu F, Nakagawa K, Klevesath M, Wilhelm S, Böhrer H, Nakagawa M, Graeff H, Martin E, Stern DM, Rosenberg RD, Ziegler R, Nawroth PP: Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity. J Clin Invest 1998, 101:1301-1309.
• [12]Horowitz NA, Blevins EA, Miller WM, Perry AR, Talmage KE, Mullins ES, Flick MJ, Queiroz KC, Shi K, Spek CA, Conway EM, Monia BP, Weiler H, Degen JL, Palumbo JS: Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain. Blood 2011, 118:2889-2895.
• [13]Van de Wouwer M, Collen D, Conway EM: Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation. Arterioscler Thromb Vasc Biol 2004, 24:1374-1383.
• [14]Stearns DJ, Kurosawa S, Esmon CT: Microthrombomodulin. Residues 310-486 from the epidermal growth factor precursor homology domain of thrombomodulin will accelerate protein C activation. J Biol Chem 1989, 264:3352-3356.
• [15]Feistritzer C, Riewald M: Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood 2005, 105:3178-3184.
• [16]Schuepbach RA, Feistritzer C, Fernández JA, Griffin JH, Riewald M: Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1. Thromb Haemost 2009, 101:724-733.
• [17]Murakami K, Okajima K, Uchiba M, Johno M, Nakagaki T, Okabe H, Takatsuki K: Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production. Am J Physiol 1997, 272:L197-L202.
• [18]Hirose K, Okajima K, Taoka Y, Uchiba M, Tagami H, Nakano K, Utoh J, Okabe H, Kitamura N: Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg 2000, 232:272-280.
• [19]Rabiet MJ, Plantier JL, Rival Y, Genoux Y, Lampugnani MG, Dejana E: Thrombin-induced increase in endothelial permeability is associated with changes in cell-to-cell junction organization. Arterioscler Thromb Vasc Biol 1996, 16:488-496.
• [20]Colotta F, Sciacca FL, Sironi M, Luini W, Rabiet MJ, Mantovani A: Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin. Am J Pathol 1994, 144:975-985.
• [21]Kaplanski G, Marin V, Fabrigoule M, Boulay V, Benoliel AM, Bongrand P, Kaplanski S, Farnarier C: Thrombin-activated human endothelial cells support monocyte adhesion in vitro following expression of intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106). Blood 1998, 92:1259-1267.
• [22]Ruf W, Furlan-Freguia C, Niessen F: Vascular and dendritic cell coagulation signaling in sepsis progression. J Thromb Haemost 2009, 7:118-121.
• [23]Wei HJ, Li YH, Shi GY, Liu SL, Chang PC, Kuo CH, Wu HL: Thrombomodulin domains attenuate atherosclerosis by inhibiting thrombin-induced endothelial cell activation. Cardiovasc Res 2011, 92:317-327.
• [24]Leung LL, Myles T, Nishimura T, Song JJ, Robinson WH: Regulation of tissue inflammation by thrombin-activatable carboxypeptidase B (or TAFI). Mol Immunol 2008, 45:4080-4083.
• [25]Villoutreix B, Dahlback B: Molecular model for the C-type lectin domain of human thrombomodulin. J Mol Model 1998, 4:310-322.
• [26]Weisel JW, Nagaswami C, Young TA, Light DR: The shape of thrombomodulin and interactions with thrombin as determined by electron microscopy. J Biol Chem 1996, 271:31485-31490.
• [27]Osorio F, e Sousa CR: Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity 2011, 34:651-664.
• [28]Conway EM, Van de Wouwer M, Pollefeyt S, Jurk K, Van Aken H, De Vriese A, Weitz JI, Weiler H, Hellings PW, Schaeffer P, Herbert JM, Collen D, Theilmeier G: The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kB and mitogen-activated protein kinase pathways. J Exp Med 2002, 196:565-577.
• [29]Huang HC, Shi GY, Jiang SJ, Shi CS, Wu CM, Yang HY, Wu HL: Thrombomodulin-mediated cell adhesion: involvement of its lectin-like domain. J Biol Chem 2003, 278:46750-46759.
• [30]Li YH, Shi GY, Wu HL: The role of thrombomodulin in atherosclerosis: from bench to bedside. Cardiovasc Hematol Agents Med Chem 2006, 4:183-187.
• [31]Scaffidi P, Misteli T, Bianchi ME: Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002, 418:191-195.
• [32]Gardella S, Andrei C, Ferrera D, Lotti LV, Torrisi MR, Bianchi ME, Rubartelli A: The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep 2002, 3:995-1001.
• [33]Czura CJ, Tracey KJ: Targeting high mobility group box 1 as a late-acting mediator of inflammation. Crit Care Med 2003, 31:S46-S50.
• [34]Abeyama K, Stern DM, Ito Y, Kawahara K, Yoshimoto Y, Tanaka M, Uchimura T, Ida N, Yamazaki Y, Yamada S, Yamamoto Y, Yamamoto H, Iino S, Taniguchi N, Maruyama I: The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism. J Clin Invest 2005, 115:1267-1274.
• [35]Ito T, Kawahara K, Okamoto K, Yamada S, Yasuda M, Imaizumi H, Nawa Y, Meng X, Shrestha B, Hashiguchi T, Maruyama I: Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes. Arterioscler Thromb Vasc Biol 2008, 28:1825-1830.
• [36]Shi CS, Shi GY, Hsiao SM, Kao YC, Kuo KL, Ma CY, Kuo CH, Chang BI, Chang CF, Lin CH, Wong CH, Wu HL: Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response. Blood 2008, 112:3661-3670.
• [37]Dauphinee SM, Karsan A: Lipopolysaccharide signaling in endothelial cells. Lab Invest 2006, 86:9-22.
• [38]Altman E, Harrison BA, Hirama T, Chandan V, To R, MacKenzie R: Characterization of murine monoclonal antibodies against Helicobacter pylori lipopolysaccharide specific for Lex and Ley blood group determinants. Biochem Cell Biol 2005, 83:589-596.
• [39]Van de Wouwer M, Plaisance S, De Vriese A, Waelkens E, Collen D, Persson J, Daha MR, Conway EM: The lectin-like domain of thrombomodulin interferes with complement activation and protects against arthritis. J Thromb Haemost 2006, 4:1813-1824.
• [40]Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G, Del-Favero J, Plaisance S, Claes B, Lambrechts D, Zoja C, Remuzzi G, Conway EM: Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med 2009, 361:345-357.
• [41]Rittirsch D, Flierl MA, Ward PA: Harmful molecular mechanisms in sepsis. Nat Rev Immunol 2008, 8:776-787.
• [42]Levi M, ten Cate H: Disseminated intravascular coagulation. N Engl J Med 1999, 341:586-592.
• [43]Nagato M, Okamoto K, Abe Y, Higure A, Yamaguchi K: Recombinant human soluble thrombomodulin decreases the plasma high-mobility group box-1 protein levels, whereas improving the acute liver injury and survival rates in experimental endotoxemia. Crit Care Med 2009, 37:2181-2186.
• [44]Saito H, Maruyama I, Shimazak S, Yamamoto Y, Aikawa N, Ohno R, Hirayama A, Matsuda T, Asakura H, Nakashima M, Aoki N: 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 2007, 5:31-41.
• [45]Ikeguchi H, Maruyama S, Morita Y, Fujita Y, Kato , Natori Y, Akatsu H, Campbell W, Okada N, Okada H, Yuzawa Y, Matsuo S: Effects of human soluble thrombomodulin on experimental glomerulonephritis. Kidney Int 2002, 61:490-501.
• [46]Ozaki T, Anas C, Maruyama S, Yamamoto T, Yasuda K, Morita Y, Ito Y, Gotoh M, Yuzawa Y, Matsuo S: Intrarenal administration of recombinant human soluble thrombomodulin ameliorates ischaemic acute renal failure. Nephrol Dial Transplant 2008, 23:110-119.
• [47]Sharfuddin AA, Sandoval RM, Berg DT, McDougal GE, Campos SB, Phillips CL, Jones BE, Gupta A, Grinnell BW, Molitoris BA: Soluble thrombomodulin protects ischemic kidneys. J Am Soc Nephrol 2009, 20:524-534.
• [48]Bollee G, Flamant M, Schordan S, Fligny C, Rumpel E, Milon M, Schordan E, Sabaa N, Vandermeersch S, Galaup A, Rodenas A, Casal I, Sunnarborg SW, Salant DJ, Kopp JB, Threadgill DW, Quaggin SE, Dussaule JC, Germain S, Mesnard L, Endlich K, Boucheix C, Belenfant X, Callard P, Endlich N, Tharaux PL: Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis. Nat Med 2011, 17:1242-1250.
• [49]Harris R: EGFR signaling in podocytes at the root of glomerular disease. Nat Med 2011, 17:1188-1189.
• [50]Kuo CH, Chen PK, Chang BI, Sung MC, Shi CS, Lee JS, Chang CF, Shi GY, Wu HL: The recombinant Lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen. Blood 2012, 119:1302-1313.
• [51]Hanyu T, Arai K, Nakano M: Urinary thrombomodulin in patients with rheumatoid arthritis: relationship to disease subset. Clin Rheumatol 1999, 18:385-389.
• [52]Conway EM, Nowakowski B: Biologically active thrombomodulin is synthesized by adherent synovial fluid cells and is elevated in synovial fluid of patients with rheumatoid arthritis. Blood 1993, 81:726-733.
• [53]Halloran MM, Carley WW, Polverini PJ, Haskell CJ, Phan S, Anderson BJ, Woods JM, Campbell PL, Volin MV, Backer AE, Koch AE: Ley/H: an endothelial-selective, cytokine-inducible, angiogenic mediator. J Immunol 2000, 164:4868-4877.
• [54]Conway EM: Thrombomodulin and its role in inflammation. Semin Immunopathol 2012, 34:107-125.
• [55]Wu KK: TM hidden treasure: lectin-like domain. Blood 2012, 119:1103-1104.