Skip to main content
SpringerLink
Log in

The Emerging Role of RAGE in Sepsis

  • Conference paper
Yearbook of Intensive Care and Emergency Medicine

Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 2006))

  • 657 Accesses

Conclusion

In conclusion, sepsis is still an important clinical challenge for ICUs with few therapeutic options. This chapter has summarized the current knowledge on RAGE, an inflammation perpetuating receptor, which plays a pivotal role in sepsis. RAGE is involved in signal transduction from pathogen substrates to cell activation during the onset of inflammation and perpetuates the immune response. Targeting this receptor might attenuate hyperinflammation. Essentially, understanding of the basic signal transduction of these receptors may offer new diagnostic and therapeutic options in septic patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bouchon A, Facchetti F, Weigand MA, Colonna M (2001) TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 410:1103–1107

    Article  CAS  PubMed  Google Scholar 

  2. Weigand MA, Horner C, Bardenheuer HJ, Bouchon A (2004) The systemic inflammatory response syndrome. Best Pract Res Clin Anaesthesiol 18:455–75

    Article  CAS  PubMed  Google Scholar 

  3. Neeper M, Schmidt AM, Brett J, et al (1992) Cloning and expression of a cell surface receptor for advanced glycosilation endproducts of proteins. J Biol Chem 267:14998–15004

    CAS  PubMed  Google Scholar 

  4. Schmidt AM, Vianna M, Gerlach M, et al (1992) Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem 267:14987–4997

    CAS  PubMed  Google Scholar 

  5. Isermann B, Bierhaus A, Humpert PM, et al (2004) AGE-RAGE: A hypothesis or a mechanism? Herz 29:504–509

    Article  PubMed  Google Scholar 

  6. Bierhaus A, Humpert PM, Morcos M, et al (2005) Understanding RAGE, the receptor for advanced glycation end products. J Mol Med 83:876–886

    Article  CAS  PubMed  Google Scholar 

  7. Huttunen HJ, Rauvala H (2004) Amphoterin as an extracellular regulator of cell motility: from discovery to disease. J Intern Med 255:351–366

    Article  CAS  PubMed  Google Scholar 

  8. Ritthaler U, Deng Y, Zhang Y, et al (1995) Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease. Am J Pathol 146:688–694

    CAS  PubMed  Google Scholar 

  9. Sousa MM, Yan SD, Stern D, Saraiva MJ (2000) Interaction of the receptor for advanced glycation end products (RAGE) with transthyretin triggers nuclear transcription factor kB (NF-kB) activation. Lab Invest 80:1101–1110

    CAS  PubMed  Google Scholar 

  10. Degryse B, Bonaldi T, Scaffidi P, et al (2001) The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. J Cell Biol 152:1197–1206

    Article  CAS  PubMed  Google Scholar 

  11. Sugaya K, Fukagawa T, Matsumoto K, et al (1994) Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 23:408–419

    Article  CAS  PubMed  Google Scholar 

  12. Hofmann MA, Drury S, Hudson BI, et al (2002) RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response. Genes Immun 3:123–135

    Article  CAS  PubMed  Google Scholar 

  13. Hofmann MA, Drury S, Fu C, et al (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901

    Article  CAS  PubMed  Google Scholar 

  14. Ishihara K, Tsutsumi K, Kawane S, Nakajima M, Kasaoka T (2003) The receptor for advanced glycation end-products (RAGE) directly binds to ERK by a D-domain-like docking site. FEBS Lett 550:107–113

    Article  CAS  PubMed  Google Scholar 

  15. Simm A, Bartling B, Silber RE (2004) RAGE: a new pleiotropic antagonistic gene? Ann N Y Acad Sci 1019:228–231

    Article  CAS  PubMed  Google Scholar 

  16. Schmidt AM, Yan SD, Yan SF, Stern DM (2000) The biology of the receptor for advanced glycation end products and ist ligands. Biochim Biophys Acta 1498:99–111

    Article  CAS  PubMed  Google Scholar 

  17. Thornalley PJ (1998) Cell activation by glycated proteins. AGE receptors, receptor recognition factors and functional classification of AGEs. Cell Mol Biol (Noisy-le-grand) 44:1013–1023

    CAS  Google Scholar 

  18. Yan SSD, Wu ZY, Zhang HP, et al (2003) Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nat Med 9:287–293

    Article  CAS  PubMed  Google Scholar 

  19. Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): Nuclear weapon in the immune arsenal. Nat Rev 5:331–342

    Article  CAS  Google Scholar 

  20. Shanmugam N, Kim YS, Lanting L, Natarajan R (2003) Regulation of cyclooxygenase-2 expression in monocytes by ligation of the receptor for advanced glycation end products. J Biol Chem 278:34834–34844

    Article  CAS  PubMed  Google Scholar 

  21. Rammes A, Roth J, Goebeler M, Klempt M, Hartmann M, Sorg C (1997) Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. J Biol Chem 272:9496–9502

    Article  CAS  PubMed  Google Scholar 

  22. Weigand MA, Volkmann M, Schmidt H, Martin E, Bohrer H, Bardenheuer HJ (2000) Neuron-specific enolase as a marker of fatal outcome in patients with severe sepsis or septic shock. Anesthesiology 92:905–907

    Article  CAS  PubMed  Google Scholar 

  23. Taguchi A, Blood DC, del Toro G, et al (2000) Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405:354–360

    Article  CAS  PubMed  Google Scholar 

  24. Andersson U, Wang H, Palmblad K, et al (2000) High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192:565–570

    Article  CAS  PubMed  Google Scholar 

  25. Wang H, Bloom O, Zhang M, et al (1999) HMGB-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251

    Article  CAS  PubMed  Google Scholar 

  26. Yang H, Ochani M, Li J, et al (2004) Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 101:296–301

    Article  CAS  PubMed  Google Scholar 

  27. Rouhiainen A, Kuja-Panula J, Wilkman E, et al (2004) Regulation of monocyte migration by amphoterin (HMGB-1). Blood 104:1174–1182

    Article  CAS  PubMed  Google Scholar 

  28. Sappington PL, Yang R, Yang H, Tracey KJ, Delude RL, Fink MP (2002) HMGB-1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice. Gastroenterology 123:790–802

    Article  CAS  PubMed  Google Scholar 

  29. Kokkola R, Andersson A, Mullins G, et al (2005) RAGE is the major receptor for the proinflammatory activity of HMGB-1 in rodent macrophages. Scand J Immunol 61:1–9

    Article  CAS  PubMed  Google Scholar 

  30. Abraham E, Arcaroli J, Carmody A, Wang H, Tracey KJ (2000) HMG-1 as a mediator of acute lung inflammation. J Immunol 165:2950–2954

    CAS  PubMed  Google Scholar 

  31. Ulloa L, Ochani M, Yang H, et al (2002) Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci USA 99:12351–12356

    Article  CAS  PubMed  Google Scholar 

  32. Liliensiek B, Weigand MA, Bierhaus A, et al (2004) Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response. J Clin Invest 113:1641–1650

    CAS  PubMed  Google Scholar 

  33. Zeng S, Feirt N, Goldstein M, et al (2004) Blockade of receptor for advanced glycation end product (RAGE) attenuates ischemia and reperfusion injury to the liver in mice. Hepatology 39:422–432

    Article  CAS  PubMed  Google Scholar 

  34. Cataldegirmen C, Zeng S, Feirt N, et al (2005) RAGE limits regeneration after massive liver injury by coordinated suppression of TNF-k and NF-kB. J Exp Med 201:473–484

    Article  CAS  PubMed  Google Scholar 

  35. Chavakis T, Bierhaus A, Al-Fakhri N, et al (2003) The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 198:1507–1515

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    M. A. Weigand, C. Bopp & B. W. Böttiger

Authors
  1. M. A. Weigand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Bopp
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. W. Böttiger
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Head) (Head)

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Weigand, M.A., Bopp, C., Böttiger, B.W. (2006). The Emerging Role of RAGE in Sepsis. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine. Yearbook of Intensive Care and Emergency Medicine, vol 2006. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-33396-7_2

Download citation

  • DOI: https://doi.org/10.1007/3-540-33396-7_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-30155-4

  • Online ISBN: 978-3-540-33396-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation