Location of Repository

The role of thrombomodulin lectin-like domain in inflammation

By Yi-Heng Li, Cheng-Hsiang Kuo, Guey-Yueh Shi and Hua-Lin Wu

Abstract

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

Topics: Review
Publisher: BioMed Central
OAI identifier: oai:pubmedcentral.nih.gov:3342133
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Preview

    Citations

    1. (1994). A: Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin.
    2. (2000). Activated protein C reduces the ischemia/ reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg
    3. (2000). AE: Ley/H: an endothelial-selective, cytokine-inducible, angiogenic mediator.
    4. (1993). Biologically active thrombomodulin is synthesized by adherent synovial fluid cells and is elevated in synovial fluid of patients with rheumatoid arthritis. Blood
    5. (2005). Characterization of murine monoclonal antibodies against Helicobacter pylori lipopolysaccharide specific for Lex and Ley blood group determinants. Biochem Cell Biol
    6. (1998). Dahlback B: Molecular model for the C-type lectin domain of human thrombomodulin.
    7. (1996). Dejana E: Thrombin-induced increase in endothelial permeability is associated with changes in cell-to-cell junction organization. Arterioscler Thromb Vasc Biol
    8. (1996). DR: The shape of thrombomodulin and interactions with thrombin as determined by electron microscopy.
    9. (2011). e Sousa CR: Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity
    10. (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
    11. (2011). EGFR signaling in podocytes at the root of glomerular disease. Nat Med
    12. (2009). EM: Thrombomodulin mutations in atypical hemolytic-uremic syndrome.
    13. (2005). Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood
    14. (2001). Endothelium-specific loss of murine thrombomodulin disrupts the protein C anticoagulant pathway and causes juvenile-onset thrombosis.
    15. (1998). 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
    16. (1988). Functionally active thrombomodulin is present in human platelets.
    17. (2008). Harmful molecular mechanisms in sepsis. Nat Rev Immunol
    18. (2008). HL: Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response. Blood
    19. (2012). HL: The recombinant Lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen. Blood
    20. (2006). HL: The role of thrombomodulin in atherosclerosis: from bench to bedside. Cardiovasc Hematol Agents Med Chem
    21. (2011). HL: Thrombomodulin domains attenuate atherosclerosis by inhibiting thrombin-induced endothelial cell activation. Cardiovasc Res
    22. (2010). HL: Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction.
    23. (2003). HL: Thrombomodulin-mediated cell adhesion: involvement of its lectin-like domain.
    24. (1987). Horiguchi S: Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation.
    25. (2008). I: Proteolytic cleavage of high mobility group box 1 protein by thrombin-thrombomodulin complexes. Arterioscler Thromb Vasc Biol
    26. (2005). I: The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism.
    27. (1987). JE: Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene. Biochemistry
    28. (2011). JS: Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain. Blood
    29. (2006). Karsan A: Lipopolysaccharide signaling in endothelial cells. Lab Invest
    30. (2002). Matsuo S: Effects of human soluble thrombomodulin on experimental glomerulonephritis. Kidney Int
    31. (1998). Miyamori I: Expression of thrombomodulin in atherosclerotic lesions and mitogenic activity of recombinant thrombomodulin in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol
    32. (2009). Molitoris BA: Soluble thrombomodulin protects ischemic kidneys.
    33. (1998). Nawroth PP: Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity.
    34. (2009). Protection of vascular barrier integrity by activated protein C in murine models depends on protease-activated receptor-1. Thromb Haemost
    35. (2009). 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
    36. (2002). Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature
    37. (1989). Residues 310-486 from the epidermal growth factor precursor homology domain of thrombomodulin will accelerate protein C activation.
    38. (2002). Rubartelli A: The nuclear protein HMGB1 is secreted by monocytes via a nonclassical, vesicle-mediated secretory pathway. EMBO Rep
    39. (2008). S: Intrarenal administration of recombinant human soluble thrombomodulin ameliorates ischaemic acute renal failure. Nephrol Dial Transplant
    40. (1997). Takatsuki K: Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production.
    41. (1999). ten Cate H: Disseminated intravascular coagulation.
    42. (2012). Tharaux PL: Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis. Nat Med
    43. (2006). The lectin-like domain of thrombomodulin interferes with complement activation and protects against arthritis. J Thromb Haemost
    44. (1987). The regulation of natural anticoagulant pathways. Science
    45. (1989). The roles of protein C and thrombomodulin in the regulation of blood coagulation.
    46. (2002). 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 mitogenactivated protein kinase pathways.
    47. (2012). Thrombomodulin and its role in inflammation. Semin Immunopathol
    48. (2004). Thrombomodulin-protein CEPCR system: integrated to regulate coagulation and inflammation. Arterioscler Thromb Vasc Biol
    49. (2012). TM hidden treasure: lectin-like domain. Blood 2012, 119:1103-1104. doi:10.1186/1423-0127-19-34 Cite this article as: Li et al.: The role of thrombomodulin lectin-like domain in inflammation.
    50. (2003). Tracey KJ: Targeting high mobility group box 1 as a late-acting mediator of inflammation. Crit Care Med
    51. (1999). Urinary thrombomodulin in patients with rheumatoid arthritis: relationship to disease subset. Clin Rheumatol
    52. (2009). Vascular and dendritic cell coagulation signaling in sepsis progression.
    53. (2008). WH: Regulation of tissue inflammation by thrombin-activatable carboxypeptidase B (or TAFI). Mol Immunol

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.