Skip to main content
SpringerLink
Log in
Book cover

Current Topics in Complement pp 189–201Cite as

The Complement System: A Potential Target for Stroke Therapy

  • Conference paper

Part of the book series: Advances in Experimental Medicine and Biology ((volume 586))

4. Conclusion

Anti-complement strategies appear to hold great promise for the development of stroke therapeutics. Yet caution should be exercised. It is clear that the complement cascade is a complex and intricate system with widely varied effects, and if any knowledge has been gained from the many failed attempts at translating stroke therapies to the bedside, it is that cavalier application of under-elucidated therapies that leads to wasted resources and the potential for poor patient outcomes.

This is a preview of subscription content, 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   259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
Price excludes VAT (USA)
  • Durable hardcover 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

5. References

  1. U. Dirnagl, C. Iadecola, M.A. Moskowitz, Pathobiology of ischaemic stroke: an integrated view, Trends Neurosci 22(9), 391–397 (1999).

    Article  PubMed  CAS  Google Scholar 

  2. D.J. Gladstone, S.E. Black, A.M. Hakim, Toward wisdom from failure: Lessons from neuroprotective stroke trials and new therapeutic directions, Stroke 33(8), 2123–2136 (2002).

    Article  PubMed  Google Scholar 

  3. B. Fischer, H. Schmoll, P. Riederer, J. Bauer, D. Platt, A. Popa-Wagner, Complement c1q and c3 mrna expression in the frontal cortex of alzheimer’s patients, J Mol Med 73(9), 465–471 (1995).

    Article  PubMed  CAS  Google Scholar 

  4. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre acute stroke trial—italy (mast-i) group, Lancet 346(8989), 1509–1514 (1995).

    Google Scholar 

  5. AstraZeneca. Astrazeneca press office announces first results from saint 1 trial. May 4, 2005

    Google Scholar 

  6. D.A. Dawson, C.A. Ruetzler, T.M. Carlos, P.M. Kochanek, J.M. Hallenbeck, Polymorphonuclear leukocytes and microcirculatory perfusion in acute stroke in the shr, Keio J Med 45(3), 248–252; discussion 252–243 (1996).

    PubMed  CAS  Google Scholar 

  7. G.J. del Zoppo, G.W. Schmid-Schonbein, E. Mori, B.R. Copeland, C.M. Chang, Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons, Stroke 22(10), 1276–1283 (1991).

    PubMed  Google Scholar 

  8. Y. Matsuo, H. Onodera, Y. Shiga, M. Nakamura, M. Ninomiya, T. Kihara, K. Kogure, Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion, Stroke 25(7), 1469–1475 (1994).

    PubMed  CAS  Google Scholar 

  9. M.M. Bednar, S. Raymond, T. McAuliffe, P.A. Lodge, C.E. Gross, The role of neutrophils and platelets in a rabbit model of thromboembolic stroke, Stroke 22(1), 44–50 (1991).

    PubMed  CAS  Google Scholar 

  10. D.L. Small, P. Morley, A.M. Buchan, Biology of ischemic cerebral cell death, Prog Cardiovasc Dis 42(3), 185–207 (1999).

    Article  PubMed  CAS  Google Scholar 

  11. M.M. Bednar, C.E. Gross, D.B. Howard, M. Lynn, Neutrophil activation in acute human central nervous system injury, Neurol Res 19(6), 588–592 (1997).

    PubMed  CAS  Google Scholar 

  12. T. Yano, S. Anraku, R. Nakayama, K. Ushijima, Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats, Anesthesiology 98(2), 465–473 (2003).

    Article  PubMed  CAS  Google Scholar 

  13. A. Shimakura, Y. Kamanaka, Y. Ikeda, K. Kondo, Y. Suzuki, K. Umemura, Neutrophil elastase inhibition reduces cerebral ischemic damage in the middle cerebral artery occlusion, Brain Research 858(1), 55–60 (2000).

    Article  PubMed  CAS  Google Scholar 

  14. M.E. Sughrue, A. Mehra, E.S. Connolly, Jr., A.L. D’Ambrosio, Anti-adhesion molecule strategies as potential neuroprotective agents in cerebral ischemia: A critical review of the literature, Inflamm Res 53(10), 497–508 (2004).

    Article  PubMed  CAS  Google Scholar 

  15. M.K. Schafer, W.J. Schwaeble, C. Post, P. Salvati, M. Calabresi, R.B. Sim, F. Petry, M. Loos, E. Weihe, Complement c1q is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia, J Immunol 164(10), 5446–5452 (2000).

    PubMed  CAS  Google Scholar 

  16. R.M. Cowell, J.M. Plane, F.S. Silverstein, Complement activation contributes to hypoxic-ischemic brain injury in neonatal rats, J Neurosci 23(28), 9459–9468 (2003).

    PubMed  Google Scholar 

  17. J. Huang, L.J. Kim, R. Mealey, H.C. Marsh, Jr., Y. Zhang, A.J. Tenner, E.S. Connolly, Jr., D.J. Pinsky, Neuronal protection in stroke by an slex-glycosylated complement inhibitory protein, Science 285(5427), 595–599 (1999).

    Article  PubMed  CAS  Google Scholar 

  18. B.P. Morgan and P. Gasque, Expression of complement in the brain: Role in health and disease, Immunol Today 17(10), 461–466 (1996).

    Article  PubMed  CAS  Google Scholar 

  19. B.P. Morgan and P. Gasque, Extrahepatic complement biosynthesis: Where, when and why? Clin Exp Immunol 107(1), 1–7 (1997).

    Article  PubMed  CAS  Google Scholar 

  20. P. Gasque, N. Julen, A.M. Ischenko, C. Picot, C. Mauger, C. Chauzy, J. Ripoche, M. Fontaine, Expression of complement components of the alternative pathway by glioma cell lines, J Immunol 149(4), 1381–1387 (1992).

    PubMed  CAS  Google Scholar 

  21. P. Gasque, A. Ischenko, J. Legoedec, C. Mauger, M.T. Schouft, M. Fontaine, Expression of the complement classical pathway by human glioma in culture. A model for complement expression by nerve cells, J Biol Chem 268(33), 25068–25074 (1993).

    PubMed  CAS  Google Scholar 

  22. J. van Beek, K. Elward, P. Gasque, Activation of complement in the central nervous system: Roles in neurodegeneration and neuroprotection, Ann NY Acad Sci 992, 56–71 (2003).

    Article  PubMed  Google Scholar 

  23. L. Belayev, R. Busto, W. Zhao, M.D. Ginsberg, Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats, Brain Res 739(1–2), 88–96 (1996).

    Article  PubMed  CAS  Google Scholar 

  24. T. Chakraborti, A. Mandal, M. Mandal, S. Das, S. Chakraborti, Complement activation in heart diseases. Role of oxidants, Cell Signal 12(9–10), 607–617 (2000).

    Article  PubMed  CAS  Google Scholar 

  25. A. Vakeva, B.P. Morgan, I. Tikkanen, K. Helin, P. Laurila, S. Meri, Time course of complement activation and inhibitor expression after ischemic injury of rat myocardium, Am J Pathol 144(6), 1357–1368 (1994).

    PubMed  CAS  Google Scholar 

  26. K.S. Kilgore, J.L. Park, E.J. Tanhehco, E.A. Booth, R.M. Marks, B.R. Lucchesi, Attenuation of interleukin-8 expression in c6-deficient rabbits after myocardial ischemia/reperfusion, J Mol Cell Cardiol 30(1), 75–85 (1998).

    Article  PubMed  CAS  Google Scholar 

  27. H.F. Weisman, T. Bartow, M.K. Leppo, H.C. Marsh Jr., G.R. Carson, M.F. Concino, M.P. Boyle, K.H. Roux, M.L. Weisfeldt, D.T. Fearon, Soluble human complement receptor type 1: In vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis, Science 249(4965), 146–151 (1990).

    Article  PubMed  CAS  Google Scholar 

  28. H.L. Lazar, T. Hamasaki, Y. Bao, S. Rivers, S.A. Bernard, R.J. Shemin, Soluble complement receptor type i limits damage during revascularization of ischemic myocardium, Ann Thorac Surg 65(4), 973–977 (1998).

    Article  PubMed  CAS  Google Scholar 

  29. M. Buerke, T. Murohara, A.M. Lefer, Cardioprotective effects of a c1 esterase inhibitor in myocardial ischemia and reperfusion, Circulation 91(2), 393–402 (1995).

    PubMed  CAS  Google Scholar 

  30. J.S. Duffield, C.F. Ware, B. Ryffel, J. Savill, Suppression by apoptotic cells defines tumor necrosis factor-mediated induction of glomerular mesangial cell apoptosis by activated macrophages, Am J Pathol 159(4), 1397–1404 (2001).

    PubMed  CAS  Google Scholar 

  31. G.L. Stahl, Y. Xu, L. Hao, M. Miller, J.A. Buras, M. Fung, H. Zhao, Role for the alternative complement pathway in ischemia/reperfusion injury. [see comment], Am J Pathol 162(2), 449–455 (2003).

    PubMed  CAS  Google Scholar 

  32. M.R. Weiser, J.P. Williams, F.D. Moore, Jr., L. Kobzik, M. Ma, H.B. Hechtman, M.C. Carroll, Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement, J Exp Med 183(5), 2343–2348 (1996).

    Article  PubMed  CAS  Google Scholar 

  33. P. Gasque, P. Chan, C. Mauger, M.T. Schouft, S. Singhrao, M.P. Dierich, B.P. Morgan, M. Fontaine, Identification and characterization of complement c3 receptors on human astrocytes, J Immunol 156(6), 2247–2255 (1996).

    PubMed  CAS  Google Scholar 

  34. P. Gasque, Y.D. Dean, E.P. McGreal, J. VanBeek, B.P. Morgan, Complement components of the innate immune system in health and disease in the cns, Immunopharmacology 49(1–2), 171–186 (2000).

    Article  PubMed  CAS  Google Scholar 

  35. P. Gasque, J.W. Neal, S.K. Singhrao, E.P. McGreal, Y.D. Dean, B.J. Van, B.P. Morgan, Roles of the complement system in human neurodegenerative disorders: pro-inflammatory and tissue remodeling activities, Mol Neurobiol 25(1), 1–17 (2002).

    Article  PubMed  CAS  Google Scholar 

  36. P. Gasque, B.P. Morgan, Complement regulatory protein expression by a human oligodendrocyte cell line: cytokine regulation and comparison with astrocytes, Immunology 89(3), 338–347 (1996).

    Article  PubMed  CAS  Google Scholar 

  37. B.P. Morgan, P. Gasque, S. Singhrao, S.J. Piddlesden, The role of complement in disorders of the nervous system, Immunopharmacology 38(1–2), 43–50 (1997).

    Article  PubMed  CAS  Google Scholar 

  38. B.P. Morgan, P. Gasque, S.K. Singhrao, S.J. Piddlesden, Role of complement in inflammation and injury in the nervous system, Exp Clin Immunogenet 14(1), 19–23 (1997).

    PubMed  CAS  Google Scholar 

  39. C.A. Rogers, P. Gasque, S.J. Piddlesden, N. Okada, V.M. Holers, B.P. Morgan, Expression and function of membrane regulators of complement on rat astrocytes in culture, Immunology 88(1), 153–161 (1996).

    Article  PubMed  CAS  Google Scholar 

  40. E. Head, B.Y. Azizeh, I.T. Lott, A.J. Tenner, C.W. Cotman, D.H. Cribbs, Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with down syndrome, Neurobiol Dis 8(2), 252–265 (2001).

    Article  PubMed  CAS  Google Scholar 

  41. Y. Matsuoka, M. Picciano, B. Malester, J. LaFrancois, C. Zehr, J.M. Daeschner, J.A. Olschowka, M.I. Fonseca, M.K. O’Banion, A.J. Tenner, C.A. Lemere, K. Duff, Inflammatory responses to amyloidosis in a transgenic mouse model of alzheimer’s disease, Am J Pathol 158(4), 1345–1354 (2001).

    PubMed  CAS  Google Scholar 

  42. P. Eikelenboom, C.E. Hack, J.M. Rozemuller, F.C. Stam, Complement activation in amyloid plaques in alzheimer’s dementia, Virchows Arch B Cell Pathol Incl Mol Pathol 56(4), 259–262 (1989).

    PubMed  CAS  Google Scholar 

  43. P.L. McGeer, H. Akiyama, S. Itagaki, E.G. McGeer, Activation of the classical complement pathway in brain tissue of alzheimer patients, Neurosci Lett 107(1–3), 341–346 (1989).

    Article  PubMed  CAS  Google Scholar 

  44. O. Yasuhara, Y. Aimi, E.G. McGeer, P.L. McGeer, Expression of the complement membrane attack complex and its inhibitors in pick disease brain, Brain Res 652(2), 346–349 (1994).

    Article  PubMed  CAS  Google Scholar 

  45. S.K. Singhrao, J.W. Neal, P. Gasque, B.P. Morgan, G.R. Newman, Role of complement in the aetiology of pick’s disease? J Neuropathol Exp Neurol 55(5), 578–593 (1996).

    PubMed  CAS  Google Scholar 

  46. M. Rancan, M.C. Morganti-Kossmann, S.R. Barnum, S. Saft, O.I. Schmidt, W. Ertel, P.F. Stahel, Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice, J Cereb Blood Flow Metab 23(9), 1070–1074 (2003).

    Article  PubMed  CAS  Google Scholar 

  47. P. Gasque, A. Thomas, M. Fontaine, B.P. Morgan, Complement activation on human neuroblastoma cell lines in vitro: route of activation and expression of functional complement regulatory proteins, J Neuroimmunol 66(1–2), 29–40 (1996).

    Article  PubMed  CAS  Google Scholar 

  48. S.K. Singhrao, J.W. Neal, N.K. Rushmere, B.P. Morgan, P. Gasque, Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis, Am J Pathol 157(3), 905–918 (2000).

    PubMed  CAS  Google Scholar 

  49. S.K. Singhrao, J.W. Neal, N.K. Rushmere, B.P. Morgan, P. Gasque, Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis, Am J Pathol 157(3), 905–918 (2000).

    PubMed  CAS  Google Scholar 

  50. A.L. D’Ambrosio, D.J. Pinsky, E.S. Connolly, The role of the complement cascade in ischemia/reperfusion injury: Implications for neuroprotection, Mol Med 7(6), 367–382 (2001).

    PubMed  CAS  Google Scholar 

  51. K. Furuya, H. Takeda, S. Azhar, R.M. McCarron, Y. Chen, C.A. Ruetzler, K.M. Wolcott, T.J. DeGraba, R. Rothlein, T.E. Hugli, G.J. del Zoppo, J.M. Hallenbeck, Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study, Stroke 32(11), 2665–2674 (2001).

    PubMed  CAS  Google Scholar 

  52. J. Vuorte, P.J. Lindsberg, M. Kaste, S. Meri, S.E. Jansson, R. Rothlein, H. Repo, Anti-icam-1 monoclonal antibody r6.5 (enlimomab) promotes activation of neutrophils in whole blood, J Immunol 162(4), 2353–2357 (1999).

    PubMed  CAS  Google Scholar 

  53. U.S. Vasthare, F.C. Barone, H.M. Sarau, R.H. Rosenwasser, M. DiMartino, W.F. Young, R.F. Tuma, Complement depletion improves neurological function in cerebral ischemia, Brain Res Bull 45(4), 413–419 (1998).

    Article  PubMed  CAS  Google Scholar 

  54. E. Figueroa, L.E. Gordon, P.W. Feldhoff, H.A. Lassiter, The administration of cobra venom factor reduces post-ischemic cerebral injury in adult and neonatal rats, Neurosci Lett 380(1–2), 48–53 (2005).

    Article  PubMed  CAS  Google Scholar 

  55. N. Akita, H. Nakase, Y. Kanemoto, T. Kaido, T. Nishioka, T. Sakaki. The effect of c 1 esterase inhibitor on ischemia: reperfusion injury in the rat brain, No To Shinkei 53(7), 641–644 (2001).

    PubMed  CAS  Google Scholar 

  56. M.G. De Simoni, C. Storini, M. Barba, L. Catapano, A.M. Arabia, E. Rossi, L. Bergamaschini, Neuroprotection by complement (c1) inhibitor in mouse transient brain ischemia, J Cereb Blood Flow Metab 23(2), 232–239 (2003).

    Article  PubMed  Google Scholar 

  57. S.M. Lew, C.E. Gross, M.M. Bednar, S.J. Russell, S.P. Fuller, C.L. Ellenberger, D. Howard, Complement depletion does not reduce brain injury in a rabbit model of thromboembolic stroke, Brain Res Bull 48(3), 325–331 (1999).

    Article  PubMed  CAS  Google Scholar 

  58. R. Gill, J.A. Kemp, C. Sabin, M.B. Pepys, Human c-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats, J Cereb Blood Flow Metab 24(11), 1214–1218 (2004).

    Article  PubMed  CAS  Google Scholar 

  59. C. Storini, E. Rossi, V. Marrella, M. Distaso, R. Veerhuis, C. Vergani, L. Bergamaschini, M.G. De Simoni, C1-inhibitor protects against brain ischemiareperfusion injury via inhibition of cell recruitment and inflammation, Neurobiol Dis 19(1–2), 10–17 (2005).

    Article  PubMed  CAS  Google Scholar 

  60. M.G. De Simoni, E. Rossi, C. Storini, S. Pizzimenti, C. Echart, L. Bergamaschini, The powerful neuroprotective action of c1-inhibitor on brain ischemia-reperfusion injury does not require c1q, Am J Pathol 164(5), 1857–1863 (2004).

    PubMed  Google Scholar 

  61. T. Wyss-Coray, F. Yan, A.H. Lin, J.D. Lambris, J.J. Alexander, R.J. Quigg, E. Masliah, Prominent neurodegeneration and increased plaque formation in complement-inhibited alzheimer’s mice, Proc Natl Acad Sci USA 99(16), 10837–10842 (2002).

    Article  PubMed  CAS  Google Scholar 

  62. D. Mevorach, Systemic lupus erythematosus and apoptosis: a question of balance, Clin Rev Allergy Immunol 25(1), 49–60 (2003).

    Article  PubMed  CAS  Google Scholar 

  63. Z. Fishelson, G. Attali, D. Mevorach, Complement and apoptosis, Mol Immunol 38(2–3), 207–219 (2001).

    Article  PubMed  CAS  Google Scholar 

  64. D. Mevorach, J.O. Mascarenhas, D. Gershov, K.B. Elkon, Complement-dependent clearance of apoptotic cells by human macrophages, J Exp Med 188(12), 2313–2320 (1998).

    Article  PubMed  CAS  Google Scholar 

  65. D. Mevorach, The immune response to apoptotic cells, Ann NY Acad Sci 887 (191–198 (1999).

    Article  PubMed  CAS  Google Scholar 

  66. D. Mevorach, Opsonization of apoptotic cells. Implications for uptake and autoimmunity, Ann NY Acad Sci 926, 226–235 (2000).

    Article  PubMed  CAS  Google Scholar 

  67. J. Savill, Apoptosis in resolution of inflammation, J Leuk Biol 61(4), 375–380 (1997).

    CAS  Google Scholar 

  68. J. Savill, Recognition and phagocytosis of cells undergoing apoptosis, Br Med Bull 53(3), 491–508 (1997).

    PubMed  CAS  Google Scholar 

  69. J. Savill, Apoptosis. Phagocytic docking without shocking [comment], Nature 392(6675), 442–443 (1998).

    Article  PubMed  CAS  Google Scholar 

  70. J. Savill, Regulation of glomerular cell number by apoptosis, Kidney Int 56(4), 1216–1222 (1999).

    Article  PubMed  CAS  Google Scholar 

  71. J. Savill, Apoptosis in resolution of inflammation, Kidney Blood Press Res 23(3–5), 173–174 (2000).

    PubMed  CAS  Google Scholar 

  72. J. Savill, Phagocyte clearance of cells dying by apoptosis and the regulation of glomerular inflammation, Adv Nephrol Necker Hosp 31, 21–28 (2001).

    PubMed  CAS  Google Scholar 

  73. Y. Ren, L. Stuart, F.P. Lindberg, A.R. Rosenkranz, Y. Chen, T.N. Mayadas, J. Savill, Nonphlogistic clearance of late apoptotic neutrophils by macrophages: efficient phagocytosis independent of beta 2 integrins, J Immunol 166(7), 4743–4750 (2001).

    PubMed  CAS  Google Scholar 

  74. J. Savill, I. Dransfield, C. Gregory, C. Haslett, A blast from the past: Clearance of apoptotic cells regulates immune responses, Nat Rev Immunol 2(12), 965–975 (2002).

    Article  PubMed  CAS  Google Scholar 

  75. J. Savill, V. Fadok, Corpse clearance defines the meaning of cell death, Nature 407(6805), 784–788 (2000).

    Article  PubMed  CAS  Google Scholar 

  76. J. Savill, C. Gregory, C. Haslett, Cell biology: eat me or die [comment], Science 302(5650), 1516–1517 (2003).

    Article  PubMed  CAS  Google Scholar 

  77. B. Knepper-Nicolai, J. Savill, S.B. Brown, Constitutive apoptosis in human neutrophils requires synergy between calpains and the proteasome downstream of caspases, J Biol Chem 273(46), 30530–30536 (1998).

    Article  PubMed  CAS  Google Scholar 

  78. U.S. Gaipl, S. Kuenkele, R.E. Voll, T.D. Beyer, W. Kolowos, P. Heyder, J.R. Kalden, M. Herrmann, Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death, Cell Death Differ 8(4), 327–334 (2001).

    Article  PubMed  CAS  Google Scholar 

  79. V.A. Fadok, D.L. Bratton, S.C. Frasch, M.L. Warner, P.M. Henson, The role of phosphatidylserine in recognition of apoptotic cells by phagocytes, Cell Death Differ 5(7), 551–562 (1998).

    Article  PubMed  CAS  Google Scholar 

  80. V.A. Fadok, P.M. Henson, Apoptosis: getting rid of the bodies, Curr Biol 8(19), R693–695 (1998).

    Article  PubMed  CAS  Google Scholar 

  81. V.A. Fadok, M.L. Warner, D.L. Bratton, P.M. Henson, Cd36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (alpha v beta 3), J Immunol 161(11), 6250–6257 (1998).

    PubMed  CAS  Google Scholar 

  82. V.A. Fadok, Clearance: The last and often forgotten stage of apoptosis, J Mammary Gland Biol Neoplasia 4(2), 203–211 (1999).

    Article  PubMed  CAS  Google Scholar 

  83. K. Elward, P. Gasque, “Eat me” and “don’t eat me” signals govern the innate immune response and tissue repair in the cns: emphasis on the critical role of the complement system, Mol Immunol 40(2–4), 85–94 (2003).

    Article  PubMed  CAS  Google Scholar 

  84. V.A. Fadok, G. Chimini, The phagocytosis of apoptotic cells, Semin Immunol 13(6), 365–372 (2001).

    Article  PubMed  CAS  Google Scholar 

  85. V.A. Fadok, Clearance: the last and often forgotten stage of apoptosis, J Mammary Gland Biol Neoplasia 4(2), 203–211 (1999).

    Article  PubMed  CAS  Google Scholar 

  86. R. De Simone, M.A. Ajmone-Cat, P. Tirassa, L. Minghetti, Apoptotic pc12 cells exposing phosphatidylserine promote the production of anti-inflammatory and neuroprotective molecules by microglial cells, J Neuropathol Exp Neurol 62(2), 208–216 (2003).

    PubMed  Google Scholar 

  87. M.Z. Ratajczak, R. Reca, M. Wysoczynski, M. Kucia, J.T. Baran, D.J. Allendorf, J. Ratajczak, G.D. Ross, Transplantation studies in c3-deficient animals reveal a novel role of the third complement component (c3) in engraftment of bone marrow cells, Leukemia 18(9), 1482–1490 (2004).

    Article  PubMed  CAS  Google Scholar 

  88. C.W. Strey, M. Markiewski, D. Mastellos, R. Tudoran, L.A. Spruce, L.E. Greenbaum, J.D. Lambris, The proinflammatory mediators c3a and c5a are essential for liver regeneration, J Exp Med 198(6), 913–923 (2003).

    Article  PubMed  CAS  Google Scholar 

  89. M.M. Markiewski, D. Mastellos, R. Tudoran, R.A. DeAngelis, C.W. Strey, S. Franchini, R.A. Wetsel, A. Erdei, J.D. Lambris, C3a and c3b activation products of the third component of complement (c3) are critical for normal liver recovery after toxic injury, J Immunol 173(2), 747–754 (2004).

    PubMed  CAS  Google Scholar 

  90. G.M. Pasinetti, G. Tocco, S. Sakhi, W.D. Musleh, M.G. DeSimoni, P. Mascarucci, S. Schreiber, M. Baudry, C.E. Finch, Hereditary deficiencies in complement c5 are associated with intensified neurodegenerative responses that implicate new roles for the c-system in neuronal and astrocytic functions, Neurobiol Dis 3(3), 197–204 (1996).

    Article  PubMed  CAS  Google Scholar 

  91. H. Osaka, P. Mukherjee, P.S. Aisen, G.M. Pasinetti, Complement-derived anaphylatoxin c5a protects against glutamate-mediated neurotoxicity, J Cell Biochem 73(3), 303–311 (1999).

    Article  PubMed  CAS  Google Scholar 

  92. P. Mukherjee, G.M. Pasinetti, Complement anaphylatoxin c5a neuroprotects through mitogen-activated protein kinase-dependent inhibition of caspase 3, J Neurochem 77(1), 43–49 (2001).

    Article  PubMed  CAS  Google Scholar 

  93. P. Mukherjee, G.M. Pasinetti, The role of complement anaphylatoxin c5a in neurodegeneration: Implications in alzheimer’s disease, J Neuroimmunol 105(2), 124–130 (2000).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, Columbia University, College of Physicians & Surgeons, New York, New York, 10032

    J Mocco, Michael E. Sughrue, Andrew F. Ducruet, Ricardo J. Komotar, Sergei A. Sosunov & E. Sander Connolly Jr.

Authors
  1. J Mocco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael E. Sughrue
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew F. Ducruet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ricardo J. Komotar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sergei A. Sosunov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Sander Connolly Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Pennsylvania, Philadelphia, PA, 19107

    John D. Lambris Ph.D. (Professor of Pathology & Laboratory Medicine) (Professor of Pathology & Laboratory Medicine)

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer Science+Business Media, LLC

About this paper

Cite this paper

Mocco, J., Sughrue, M.E., Ducruet, A.F., Komotar, R.J., Sosunov, S.A., Connolly, E.S. (2006). The Complement System: A Potential Target for Stroke Therapy. In: Lambris, J.D. (eds) Current Topics in Complement. Advances in Experimental Medicine and Biology, vol 586. Springer, Boston, MA. https://doi.org/10.1007/0-387-34134-X_13

Download citation

Publish with us

Policies and ethics

Search

Navigation