Host Cell Protection from Complement by Glycosyl-phosphatidylinositol-Anchored Complement Inhibitors and Their Deficiencies in Paroxysmal Nocturnal Hemoglobinuria

  • T. Kinoshita


Complement plays an essential role in eliminating microorganisms and immune-complexes from tissues and blood. Its three major functions are targeting microorganisms to cells bearing complement receptors, recruiting phagocytic cells to the area where complement activation is taking place and destruction of target membranes. Since these effector functions mediated by C3 and C5 convertases and membrane attack complexes (MAC) are very effective, activation of complement should be focused on target surfaces. However, an inherent characteristics of complement is that its active fragments or their complexes, such as C4b, C3b and C5b-7, can bind to host cell surfaces and lead to host cell damage. This potentially harmful characteristics is prevented by widely distributed membrane-bound complement inhibitors that protect host cells from the action of autologous complement by inhibiting C3 and C5 convertases and MAC.


Paroxysmal Nocturnal Hemoglobinuria Membrane Attack Complex Complement Inhibitor Host Cell Surface Erythrocyte Membrane Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Asch AS, Kinoshita T, Jaffe EA, Nussenzweig V (1986) J Exp Med 163:221–226CrossRefPubMedGoogle Scholar
  2. Auditore JV, Hartmann RC, Flexner JM, Balchum OJ (1969) Arch Pathol 69:534–543Google Scholar
  3. Beck WS, Valentine WN (1951) J Lab Clin Med 38:245–253PubMedGoogle Scholar
  4. Blaas P, Berger B, Weber S, Peter HH, Hansch GM (1988) J Immunol 140:3045–3051PubMedGoogle Scholar
  5. Caras IW, Davitz MA, Rhee L, Weddell G, Martin Jr DW, Nussenzweig V (1987) Nature 325:545–549CrossRefPubMedGoogle Scholar
  6. Davitz MA, Low MG, Nussenzweig V (1986) J Exp Med 163:1150–1161CrossRefPubMedGoogle Scholar
  7. Ferguson MAJ, Williams AF (1988) Ann Rev Biochem 57:285–320CrossRefPubMedGoogle Scholar
  8. Fujita T, Inoue T, Ogawa K, Iida K, Tamura N (1987) J Exp Med 166:1221–1228CrossRefPubMedGoogle Scholar
  9. Hansch GM, Schonermark S, Roelcke D (1987) J Clin Invest 80:7–12PubMedCentralCrossRefPubMedGoogle Scholar
  10. Hansch GM, Weller PF, Nicholson-Weller A (1988) Blood 72:1089–1092PubMedGoogle Scholar
  11. Haziot A, Chen S, Ferrero E, Low MG, Silber R, Goyert SM (1988) J Immunol 141:547–552PubMedGoogle Scholar
  12. Holguin MH, Fredrick LR, Bernshaw NJ, Wilcox LA, Parker CJ (1989) J Clin Invest 84:in pressGoogle Scholar
  13. Holguin MH, Wilcox LA, Bernshaw NJ, Rosse WF, Parker CJ Submitted for publicationGoogle Scholar
  14. Huizinga TW, Schoot van der CL, Jost C, Klaasssen R, Kleijer M, Borne von dem AEGK, Roos D, Tetteroo AT (1988) Nature 333:667–669CrossRefPubMedGoogle Scholar
  15. Kanamaru A, Okuda K, Ueda E, Kitani T, Kinoshita T, Nagai K (1988) Blood 72:507–511PubMedGoogle Scholar
  16. Kinoshita T, Medof ME, Silber R, Nussenzweig V (1985) J Exp Med 162:75–92CrossRefPubMedGoogle Scholar
  17. Kinoshita T, Medof ME, Nussenzweig V (1986) J Immunol 136:3390–3395PubMedGoogle Scholar
  18. Kinoshita T, Rosenfeld SI, Nussenzweig V (1987) J Immunol 138:2294–2298Google Scholar
  19. Kunstling TR, Rosse WF (1969) Blood 33:607–616PubMedGoogle Scholar
  20. Lewis SM, Dacie JV (1965) Br J Haematol 11:549–556CrossRefPubMedGoogle Scholar
  21. Low MG (1989) FASEB J 3:1600–1608PubMedGoogle Scholar
  22. Martin DE, Zalman LS, Müller-Eberhard HJ (1988) Proc Natl Acad Sci USA 85:213–217PubMedCentralCrossRefPubMedGoogle Scholar
  23. Medof ME, Kinoshita T, Nussenzweig V (1984) J Exp Med 160:1558–1578CrossRefPubMedGoogle Scholar
  24. Medof ME, Kinoshita T, Silber R, Nussenzweig V (1985) Proc Natl Acad Sci USA 83:2980–2984CrossRefGoogle Scholar
  25. Medof ME, Walter EI, Roberts WL, Haas R, Rosenberry TL (1986) Biochemistry 25:6740–6747CrossRefPubMedGoogle Scholar
  26. Medof ME, Gottlieb A, Kinoshita T, Hall S, Silber R, Nussenzweig V, Rosse WF (1987a) J Clin Invest 80:165–174PubMedCentralCrossRefPubMedGoogle Scholar
  27. Medof ME, Lublin DM, Holers VM, Ayers DJ, Getty RR, Leykam JF, Atkinson JP, Tykocinski ML (1987b) Proc Natl Acad Sci USA 84:2007–2011PubMedCentralCrossRefPubMedGoogle Scholar
  28. Medof ME, Walter EI, Rutgers JL, Knowles DM, Nussenzweig V (1987c) J Exp Med 165:848–864CrossRefPubMedGoogle Scholar
  29. Merry AH, Sim RB, Uchikawa M, Rawlinson VI, Spring FA, Parsons SF, Daha M (1988) Complement 5:190Google Scholar
  30. Moore JG, Frank MM, Müller-Eberhard HJ, Young NS (1985) J Exp Med 162:1182–1192CrossRefPubMedGoogle Scholar
  31. Müller-Eberhard HJ, Zalman LS, Chiu FJ, Jung G, Martin DE (1986) Prog Immunol 6:268–281CrossRefGoogle Scholar
  32. Müller-Eberhard HJ (1988) Immunol Rev 103:87–98CrossRefPubMedGoogle Scholar
  33. Nicholson-Weller A, Bürge J, Fearon DT, Weller PF, Austen KF (1982) J Immunol 129:184–189PubMedGoogle Scholar
  34. Nicholson-Weller A, March JP, Rosenfeld SI, Austen KF (1983) Proc Natl Acad Sci USA 80:5066–5070PubMedCentralCrossRefPubMedGoogle Scholar
  35. Nicholson-Weller A, Spicer DB, Austen KF (1985a) New Eng J Med 312:1091–1097CrossRefPubMedGoogle Scholar
  36. Nicholson-Weller A, March JP, Rosen CE, Spicer DB, Austen KF (1985b) Blood 65:1237–1244PubMedGoogle Scholar
  37. Ninomiya H, Abe T, Shichishima T, Terasawa T, Fujita T (1988) Br J Haematol 69:81–87CrossRefPubMedGoogle Scholar
  38. Okada H, Nagami Y, Takahashi K, Okada N, Hideshima T, Takizawa H, Kondo J Biochem Biophys Res Comm in pressGoogle Scholar
  39. Okada N, Harada R, Fujita T, Okada H (1989a) Inter Immunol 1:205–208CrossRefGoogle Scholar
  40. Okada N, Harada R, Fujita T, Okada H (1989b) J Immunol in pressGoogle Scholar
  41. Oni SB, Osunkoya BO, Luzzatto L (1970) Blood 36:145–152PubMedGoogle Scholar
  42. Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983) Proc Natl Acad Sci USA 80:5430–5434PubMedCentralCrossRefPubMedGoogle Scholar
  43. Quigg RJ, Nicholson-Weller A, Cybulsky AV, Badalamenti J, Salant DJ (1989) J Immunol 142:877–882PubMedGoogle Scholar
  44. Reid KBM, Day AJ (1989) Immunol Today 10:177–180CrossRefPubMedGoogle Scholar
  45. Rosse WF, Parker CJ (1985) Clin Haematol 14:105–125PubMedGoogle Scholar
  46. Schönermark S, Rauterberg EW, Shin ML, Loke S, Roelcke D, Hansch GM (1 986) J Immunol 136:1772–1776PubMedGoogle Scholar
  47. Schönermark S, Filsinger S, Berger B, Hansch GM (1988) Immunology 63:585–590PubMedCentralPubMedGoogle Scholar
  48. Selvaraj P, Dustin ML, Silber R, Low MG, Springer TA (1987) J Exp Med 166:1011–1025CrossRefPubMedGoogle Scholar
  49. Selvaraj P, Rosse WF, Silber R, Springer TA (1988) Nature 333:565–567CrossRefPubMedGoogle Scholar
  50. Shaw S (1989) Nature 338:539–540CrossRefPubMedGoogle Scholar
  51. Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B (1989) Blood 73:284–289PubMedGoogle Scholar
  52. Spring FA, Judson PA, Daniels GL, Parsons SF, Mallinson G, Anstee DJ (1987) Immunology 62:307–313PubMedCentralPubMedGoogle Scholar
  53. Stefanova I, Hilgert I, Kristofova H, Brown R, Low MG, Horejsi V (1989) Mol Immunol 26:153–161CrossRefPubMedGoogle Scholar
  54. Sugita Y, Nakano Y, Tomita M (1988) J Biochem 104:633–637PubMedGoogle Scholar
  55. Sugita Y, Mazda T, Tomita M (1989) J Biochem in pressGoogle Scholar
  56. Telen MJ, Hall SE, Green AM, Moulds JJ, Rosse WF (1988) J Exp Med 167:1993–1998PubMedCentralCrossRefPubMedGoogle Scholar
  57. Thomas J, Webb W, Davitz MA, Nussenzweig V (1987) Biophysic J 51:522aGoogle Scholar
  58. Ueda E, Kinoshita T, Nojima J, Inoue K, Kitani T (1989) J Immunol in pressGoogle Scholar
  59. Ueda E, Kinoshita T, Terasawa T, Shichishima T, Inoue K, Kitani T Submitted for publicationGoogle Scholar
  60. Zalman LS, Wood LM, Müller-Eberhard HJ (1986) Proc Natl Acad Sci USA 83:6975–6979PubMedCentralCrossRefPubMedGoogle Scholar
  61. Zalman LS, Wood LM, Frank MM, Müller-Eberhard (1987) J Exp Med 165:572–577CrossRefPubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1989

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  • T. Kinoshita

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