Skip to main content
SpringerLink
Log in

Molecular Mechanisms of Complement Activation during Ischemia and Reperfusion

  • Conference paper
Yearbook of Intensive Care and Emergency Medicine 2002

Part of the book series: Yearbook of Intensive Care and Emergency Medicine 2002 ((YEARBOOK,volume 2002))

  • 137 Accesses

Abstract

Ischemia is a frequent clinical problem occurring, amongst others, in myocardial infarction, transplantation, vascular surgery, and thromb-embolic disease. The obvious treatment of ischemia is reperfusion of the jeopardized organ or tissue. However, when ischemia is too severe, reperfusion may exacerbate rather than limit tissue damage, a phenomenon known as ischemia/reperfusion (I/R)-injury. A number of studies have been performed to unravel the pathophysiology of I/R-injury, and it is now clear that this condition is mainly due to an inflammatory process elicited by reperfusion. Hence, limiting I/R-induced inflammatory reactions is expected to improve the efficacy of reperfusion. Indeed, inhibition of inflammatory mediators improves the beneficial effects of reperfusion of ischemic tissues in animal models. In this chapter we will summarize the role of inflammation in the pathogenesis of I/R-injury, and discuss in more detail that of the complement system, as this plasma cascade system seems to be a key mediator in this condition.

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 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

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. Li C, Browder W, Kao RL (1999) Early activation of transcription factor NF-кB during ischemia in reperfused rat heart. Am J Physiol 276:H543–H552 (Abst)

    PubMed  CAS  Google Scholar 

  2. Konturek PC, Duda A, Brzozowski T, et al (2000) Activation of genes for superoxide dismu-tase, interleukin-1β, tumor necrosis factor-alpha and intercellular adhesion molecule-1 during healing of ischemia-reperfusion-induced gastric injury. Scand J Gastroenterol 35: 452–463

    Article  PubMed  CAS  Google Scholar 

  3. Seekamp A, Warren JS, Remick DG, Till GO, Ward PA (1993) Requirements for tumor necrosis factor-alpha and interleukin-1 in limb ischemia/reperfusion injury and associated lung injury. Am J Pathol 143:453–463

    PubMed  CAS  Google Scholar 

  4. Steinberg JB, Kapelanski DP, Olson JD, Weiler JM (1993) Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 106:1008–1016

    PubMed  CAS  Google Scholar 

  5. Yang Z, Zingarelli B, Szabo C (2000) Crucial role of endogenous IL-10 production in myocardial ischemia reperfusion injury. Circulation 101:1019–1026

    Article  PubMed  CAS  Google Scholar 

  6. Zund G, Nelson DP, Neufeld EJ et al (1996) Hypoxia enhances stimulus-dependent induction of E-selectin on aortic endothelial cells. Proc Natl Acad Sei USA 93:7075–7080

    Article  CAS  Google Scholar 

  7. Lindsay TF, Hill J, Ortiz F et al (1992) Blockade of complement activation prevents local and pulmonary albumin leak after lower torso ischemia-reperfusion. Ann Surg 216:677–683

    Article  PubMed  CAS  Google Scholar 

  8. Seekamp A, Mulligan MS, Till GO, et al (1993) Role of β2 integrins and ICAM-1 in lung injury following ischemia-reperfusion of rat hind limb. Am J Pathol 143:464–472

    PubMed  CAS  Google Scholar 

  9. Lucchesi BR, Kilgore KS (1997) Complement inhibitors in myocardial ischemia/reperfusion injury. Immunopharmacology 38:27–42

    Article  PubMed  CAS  Google Scholar 

  10. Entman ML, Michael L, Rossen RD, et al (1991) Inflammation in the course of early myocardial ischemia. Faseb J 5:2529–2537

    PubMed  CAS  Google Scholar 

  11. Cines DB, Pollak ES, Buck CA, et al (1998) Endothelial Cells in Physiology and in the Pathophysiology of vascular disorders. Blood 91:3527–3561

    PubMed  CAS  Google Scholar 

  12. Silverstein RL (1999) The vascular endothelium. In: Gallin JI, Snyderman R, Haynes BF (eds) Inflammation: Basic Principles and Clinical Correlates. 3rd edition, Lipincott Williams & Wilkins, Philadelphia, pp 207–225

    Google Scholar 

  13. Iwahori Y, Ishiguro N, Shimizu T, et al (1998) Selective neutrophils depletion with monoclonal antibody attenuates I/R injury in skeletal muscle. J Reconstr Microsurg 14:109–116

    Article  PubMed  CAS  Google Scholar 

  14. Zhao ZQ, Lefer DJ, Sato H, Hart KK, Jefforda PR, Vinten-Johansen J (1997) Monoclonal antibody to ICAM-1 preserves postischemic blood flow and reduces infarct size after ischemia-reperfusion in rabbit. J Leukoc Biol 62:292–300

    PubMed  CAS  Google Scholar 

  15. Cooper NL (1999) Biology of the complement system. In: Gallin JI, Snyderman R, Haynes BF (eds) Inflammation: Basic Principles and Clinical Correlates. 3rd edition, Lipincott Williams & Wilkins, Philadelphia, pp 281–307

    Google Scholar 

  16. Wolbink GJ, Brouwer MC, Buysmann S, Ten Berge IJM, Hack CE (1996) CRP-mediated activation of complement in vivo. J Immunol 157:473–479

    PubMed  CAS  Google Scholar 

  17. Vakeva AP, Agah A, Rollins SA, et al (1998) Myocardial infarction and apoptosis after myocardial ischemia and reperfusion. Role of the terminal complement components and inhibition by anti-C5 therapy. Circulation 97:2259–2267

    Article  PubMed  CAS  Google Scholar 

  18. Tedesco F, Pausa M, Nardon E, Introna M, Mantovani A, Dobrina A (1997) The cytolytically inactive terminal complement complex activates endothelial cells to express adhesion molecules and tissue factor procoagulant activity. J Exp Med 185:1619–1627

    Article  PubMed  CAS  Google Scholar 

  19. Agostoni A, Gardinali M, Frangi D, et al (1994) Thrombolytic treatment and complement activation. Ann Ital Med Int 9:178–179

    PubMed  CAS  Google Scholar 

  20. Marks RM, Todd III RF, Ward PA (1989) Rapid induction of neutrophil-endothelial adhesion by endothelial complement fixation. Nature 339:314–317

    Article  PubMed  CAS  Google Scholar 

  21. Vakeva A, Meri S (1998) Complement activation and regulator expression after anoxic injury of human endothelial cells. APMIS 106:1149–1156

    Article  PubMed  CAS  Google Scholar 

  22. Chenoweth DE, Cooper SW, Hugh TE, Steward RW, Blackstone EH, Kirklin JW (1981) Complement activation during cardio-pulmonary bypass. Evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 304:497–503

    Article  PubMed  CAS  Google Scholar 

  23. Jones J, Morgan BP (1995) Apoptosis is associated with reduced expression of complement regulatory molecules, adhesion molecules and other receptors on polymorphonuclear leucocytes: functional and role in inflammation. Immunology 86:651–660

    PubMed  CAS  Google Scholar 

  24. Weisman HF, Bartow T, Leppo MK, et al (1990) Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing postischemic myocardial inflammation and necrosis. Science 249:146–151

    Article  PubMed  CAS  Google Scholar 

  25. Soarzec JY, Delautier D, Moreau A, et al (1994) Expression of complement-regulatory proteins in normal and UW-preserved human liver. Gastroenterology 107:505–516

    Google Scholar 

  26. Brooimans RA, Van der Ark AAJ, Tomita M, Van Es LA, Daha M (1992) CD59 expressed by human endothelial cells functions as a protective molecule against complement-mediated lysis. Eur J Immunol 22:791–797

    Article  PubMed  CAS  Google Scholar 

  27. Vakeva A, Morgan BP, Tikkanen I, Helin K, Laurila P, Meri S (1994) Time course of complement activation and inhibitor expression after ischemic injury of rat myocardium. Am J Pathol 144:1357–1368

    PubMed  CAS  Google Scholar 

  28. Vakeva A, Lehto T, Takala A, Meri S (2000) Detection of a soluble form of the complement membrane attack complex inhibitor CD59 in plasma after acute myocardial infarction. Scand J Immunol 52:411–414

    Article  PubMed  CAS  Google Scholar 

  29. Collard CD, Vakeva A, Bukusoglu C, et al (1997) Reoxygenation of hypoxic human umbilical vein endothelial cells activates the classic complement pathway. Circulation 96:326–333

    Article  PubMed  CAS  Google Scholar 

  30. Collard CD, Bukusoglu C, Agah A, et al (1999) Hypoxia-induced expression of complement receptor type 1 (CR1, CD35) in human vascular endothelial cells. Am J Physiol 276:C450–C458

    PubMed  CAS  Google Scholar 

  31. Hill JH, Ward PA (1971) The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats. J Exp Med 133:885–900

    Article  PubMed  CAS  Google Scholar 

  32. Horstick G, Heimann A, Götze O, et al (1997) Intracoronary application of cl esterase inhibitor improves cardiac function and reduces myocardial necrosis in an experimental model of ischemia and reperfusion. Circulation 95:701–708

    Article  PubMed  CAS  Google Scholar 

  33. Buerke M, Prüfer D, Dahm M, et al (1998) Blocking of classical complement pathway inhibits endothelial adhesion molecule expression and preserves ischemic myocardium from reperfusion injury. J Pharmacol Exp Ther 286:429–438

    PubMed  CAS  Google Scholar 

  34. Lehmann TG, Koeppel TA, Kirschfink M, et al (1998) Complement inhibition by soluble complement receptor type 1 improves microcirculation after rat liver transplantation. Transplantation 66:717–722

    Article  PubMed  CAS  Google Scholar 

  35. Eror AT, Stojadinovic A, Starnes BW, et al (1999) Antiinflammatory effects of soluble complement receptor type 1 promote rapid recovery of ischemia/reperfusion injury in rat small intestine. Clin Immunol 90:266–275

    Article  PubMed  CAS  Google Scholar 

  36. Lazar HL, Bao Y, Gaudiani J, et al (1999) Total complement inhibition: An effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass. Circulation 100:1438–1442

    Article  PubMed  CAS  Google Scholar 

  37. Maroko PR, Carpenter CB, Chariello M (1978) Reduction by cobra venom factor of myocardial necrosis after coronary artery occlusion. J Clin Invest 61:661–670

    Article  PubMed  CAS  Google Scholar 

  38. Ikai M, Itoh M, Joh T, et al (1996) Complement plays an essential role in shock following intestinal ischaemia in rats. Clin Exp Immunol 106:156–159

    Article  PubMed  CAS  Google Scholar 

  39. Kroshus TJ, Salerno CT, Yeh CG, et al (2000) A recombinant soluble chimeric complement inhibitor composed of human cd46 and cd55 reduces acute cardiac tissue injury in models of pig-human heart transplantation. Transplantation 69:2282–2289

    Article  PubMed  CAS  Google Scholar 

  40. Heller T, Hennecke M, Baumann U et al (1999) Selection of C5a receptor antagonist from phage libraries attenuating the inflammatory response in immune complex disease and ischemia/reperfusion injury. J Immunol 163:985–994

    PubMed  CAS  Google Scholar 

  41. Fitch JCK, Rollins S, Matis L, et al (1999) Pharmacology and biological efficacy of recombinant, humanized, single-chain antibody c5 complement inhibitor in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. Circulation 100:2499–2506

    Article  PubMed  CAS  Google Scholar 

  42. Collard CD, Agah A, Reenstra W, Buras J, Stahl GL (1999) Endothelial nuclear factor-кЬ translocation and vascular cell adhesion molecule-1 induction by complement: inhibition with anti-human C5 therapy or cGMP analogues. Arterioscler Thromb Vase Biol 19:2623–2629

    Article  CAS  Google Scholar 

  43. Kyriakides C, Austen W, Wang Y, et al (1999) Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex. Am J Physiol 277:1263–1268

    Google Scholar 

  44. Collard CD, Lebowski R, Jordan JE, Agah A, Stahl GL (1999) Complement activation following oxidative stress. Mol Immunol 36:941–948

    Article  PubMed  CAS  Google Scholar 

  45. Weiser MR, Williams JP, Moore FD, et al (1996) Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement. J Exp Med 183:2343–2348

    Article  PubMed  CAS  Google Scholar 

  46. Williams JP, Pechet TTV, Weiser MR, et al (1999) Intestinal reperfusion injury is mediated by IgM and complement. J Appl Physiol 86:938–942

    PubMed  CAS  Google Scholar 

  47. Suankratay C, Mold C, Zhang Y, et al (1998) Complement regulation in innate immunity and the acute-phase response: inhibition of mannan-binding lectin-initiated complement cytolysis by C-reactive protein (CRP). Clin Exp Immunol 113:353–359

    Article  PubMed  CAS  Google Scholar 

  48. Volanakis JE, Narkates AJ (1981) Interaction of C-reactive protein with artificial phosphatidylcholine bilayers and complement. J Immunol 126:1820–1825

    PubMed  CAS  Google Scholar 

  49. Lagrand WK, Visser CA, Hermens WT et al (1999) C-Reactive protein as a cardiovascular risk factor. More than epiphenomenon? Circulation 100:96–102

    Article  PubMed  CAS  Google Scholar 

  50. Lagrand WK, Niessen HWM, Wolbink GJ, et al (1997) C-Reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 95(1):97–103

    Article  PubMed  CAS  Google Scholar 

  51. Griselli M, Herbert J, Hutchinson WL, et al (1999) C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 190:1733–1740

    Article  PubMed  CAS  Google Scholar 

  52. Pasceri V, Willerson JT, Yeh ETH (2000) Direct proinflammatory effect of c-reactive protein on human endothelial cells. Circulation 102:2165–2168

    Article  PubMed  CAS  Google Scholar 

  53. Kagiyama A, Savage HE, Michael LH, Hanson G, Entman ML, Rossen RD (1989) Molecular basis of complement activation in ischemic myocardium: identification of specific molecules of mitochondrial origin that bind human Clq and fix complement. Circ Res 64:607–615

    Article  PubMed  CAS  Google Scholar 

  54. Rossen RD, Michael LH, Hawkins HK, et al (1994) Cardiolipin-protein complexes and initiation of complement activation after coronary artery occlusion. Circ Res 75:546–555

    Article  PubMed  CAS  Google Scholar 

  55. Giclas PC, Pinckard RN, Olson MS (1979) In vitro activation of complement by isolated human heart subcellular membranes. J Immunol 122:146–151

    PubMed  CAS  Google Scholar 

  56. Collard CD, Vakeva A, Morrissey MA, et al (2000) Complement activation after oxidative stress: role of the lectin complement pathway. Am J Pathol 156: 1549–1556

    Article  PubMed  CAS  Google Scholar 

  57. Collard CD, Montaldo MC, Reenstra WR, Buras JA, Stahl GL (2001) Endothelial oxidative stress activates the lectin complement pathway; role of cytokeratin 1. Am J Pathol 159:1045–1054

    Article  PubMed  CAS  Google Scholar 

  58. Jordan JE, Montaldo MC, Stahl GL (2001) Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury. Circulation 104:1413–1418

    Article  PubMed  CAS  Google Scholar 

  59. Salama A, Hugo FH, Heinrich D, et al (1988) Deposition of terminal C5b-9 complement complexes on erythrocytes and leukocytes during cardiopulmonary bypass. N Engl J Med 318:408–414

    Article  PubMed  CAS  Google Scholar 

  60. Hostetter MK, Johnson GM (1989) The erythrocytes as instigator of inflammation. J Clin Invest 84:665–671

    Article  PubMed  CAS  Google Scholar 

  61. Test ST, Mitsuyoshi J (1997) Activation of the alternative pathway of complement by calcium-loaded erythrocytes resulting from loss of membrane phospholipid asymmetry. J Lab Clin Med 130:169–182

    Article  PubMed  CAS  Google Scholar 

  62. Hindsmarsh EJ, Marks RM (1998) Complement activation occurs on subendothelial extracellular matrix in vitro and is initiated by retraction or removal of overlying endothelial cells. J Immunol 160:6128–6136

    Google Scholar 

  63. Mold C, Morris CA (2001) Complement activation by apoptotic endothelial cells following hypoxia/reoxygenation. Immunology 102:359–364

    Article  PubMed  CAS  Google Scholar 

  64. Familian A, Zwart B, Huisman HG, et al (2001) Chromatin-independent binding of serum amyloid P component to apoptotic cells. J Immunol 167:647–654

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. C. L. F. Ciurana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. E. Hack
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

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

    Jean-Louis Vincent (Head, Department of Intensive Care) (Head, Department of Intensive Care)

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ciurana, C.L.F., Hack, C.E. (2002). Molecular Mechanisms of Complement Activation during Ischemia and Reperfusion. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine 2002. Yearbook of Intensive Care and Emergency Medicine 2002, vol 2002. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56011-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-56011-8_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-43149-7

  • Online ISBN: 978-3-642-56011-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation