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Decay-Accelerating Factor and Membrane Cofactor Protein

  • D. M. Lublin
  • J. P. Atkinson
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 153)

Abstract

Cells exposed to plasma proteins are frequently under attack from the complement system. This can arise either as a bystander process to the classical or alternative pathways of activation initiated during the immune response to foreign particles and organisms or from the constant tick-over of the alternative pathway. Thus, it is critical for the cell to regulate the complement pathway on its own surface. The plasma proteins, H and C4 binding protein (C4bp), in conjugation with the serine protease I, function to this end. Additionally, cells possess a number of membrane proteins to regulate complement deposited on their surfaces; the largest group, focused on C3 and the C3 convertases, consists of the C3b/C4b receptor (CR1), decay-accelerating factor (DAF), and membrane cofactor protein (MCP). CR1, although it has both decay-accelerating activity and serves as a cofactor for the I-mediated cleavage of C3b and C4b, acts mainly extrinsically as a receptor for C3b-bearing immune complexes. DAF exerts its decay-accelerating activity intrinsically on the cell itself (see below). Indeed, the lack of DAF in the membrane of blood cells in the disease paroxysmal nocturnal hemoglobinuria (PNH) leads to an increased complement sensitivity of these cells. Purified MCP can also regulate C3 and the C3 convertases through cofactor I activity. MCP has the same approximate size and overall structure as DAF, and hence it might also function intrinsically to control C3 convertases formed on the same cell. This chapter reviews in detail the structure, both at the protein and DNA levels, of these two complement regulatory membrane glycoproteins, DAF and MCP, and discusses their physiological roles in protecting cells from damage by autologous complement.

Keywords

Paroxysmal Nocturnal Hemoglobinuria Membrane Cofactor Protein Cofactor Activity Complement Regulatory Protein Paroxysmal Nocturnal Hemoglobinuria Patient 
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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References

  1. Asch AS, Kinoshita T, Jaffe EA, Nussenzweig V (1986) Decay-accelerating factor is present on cultured human umbilical vein endothelial cells. J Exp Med 163: 221–226PubMedCrossRefGoogle Scholar
  2. Atkinson JP, Fames T (1987) Separation of self from non-self in the complement system. Immunol Today 8: 212–215CrossRefGoogle Scholar
  3. Auditore JV, Hartmann RC (1959) Paroxysmal nocturnal hemoglobinuria II. Erythrocyte acetylcholinesterase defect. Am J Med 27: 401–410PubMedCrossRefGoogle Scholar
  4. Ballard L, Seya T, Teckman J, Lublin DM, Atkinson JP (1987) A polymorphism of the complement regulatory protein MCP (membrane cofactor protein or gp45–70). J Immunol 138: 3850–3855PubMedGoogle Scholar
  5. Ballard LL, Bora NS, Yu GH, Atkinson JP (1988) Biochemical characterization of membrane cofactor protein of the complement system. J Immunol 141: 3923–3929PubMedGoogle Scholar
  6. Boothroyd JC, Paynter CA, Cross GAM, Bernards A, Borst P (1981) Variant surface glycopro-teins of Trypanosoma bruce. are synthesized with cleavable hydrophobic sequences at the carboxy and amino termini. Nucl Acids Res 9: 4735–4743PubMedCrossRefGoogle Scholar
  7. Bora NS, Lublin DM, Kumar BV, Hockett RD, Holers VM, Atkinson JP (1989) Structural gene for human membrane cofactor protein (MCP) of complement maps to within 100 kb of the 3’ and of the C3b/C4b receptor gene. J Exp Med 169: 597–602PubMedCrossRefGoogle Scholar
  8. Caras IW, Davitz MA, Rhee L, Weddell G, Martin DW, Nussenzweig V (1987a) Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins. Nature 325: 545–549PubMedCrossRefGoogle Scholar
  9. Caras IW, Weddell GN, Davitz MA, Nussenzweig V, Martin DW (1987b) Signal for attachment of a phospholipid membrane anchor in decay-accelerating factor. Science 238: 1280–1283PubMedCrossRefGoogle Scholar
  10. Carroll MC, Alicot EM, Katzman PJ, Klickstein LB, Smith JA, Fearon DT (1988) Organization of the genes encoding complement receptors type 1 and 2, decay accelerating factor, and C4-binding protein in the RCA locus on human chromosome 1. J Exp Med 167:1271–1280PubMedCrossRefGoogle Scholar
  11. Cole J, Housley GA, Dykman TR, MacDermott RP, Atkinson JP (1985) Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines. Proc Natl Acad Sci USA 83: 859–863CrossRefGoogle Scholar
  12. Davis CG, Elhammer A, Russell DW, Schneider WJ, Kornfeld S, Brown MS, Goldstein JL (1986) Deletion of clustered O-linked carbohydrates does not impair function of low density lipoprotein receptor in transfected fibrolasts. J Biol Chem 262: 2828–2838Google Scholar
  13. Davitz MA, Low MG, Nussenzweig V (1986) Release of decay-accelerating factor (DAF) from the cell membrane by phosphatidylinositol-specific phospholipase C (PIPLC). Selective modification of a complement regulatory protein. J Exp Med 163: 1150–1161PubMedCrossRefGoogle Scholar
  14. Davitz MA, Hereld D, Shak S, Krakow J, Englund PT, Nussenzweig V (1987) A glycan-phos-phatidylinositol-specific phospholipase D in human serum. Science 238: 81–84PubMedCrossRefGoogle Scholar
  15. Dixit R, Schneider R, Law SK, Kulczycki A, Atkinson JP (1981) Ligand binding specificity of a rabbit alveolar macrophage receptor for C3b. J Biol Chem 257: 1595–1597Google Scholar
  16. Ferguson MAJ, Homans SW, Dwek RA, Rademacher TW (1988) Glycosyl-phosphatidylinositol moiety that anchors Trypanosoma bruce. variant surface glycoprotein to the membrane. Science 239: 753–759PubMedCrossRefGoogle Scholar
  17. Ferguson MAJ, Williams AF (1988) Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structure. Annu Rev Biochem 57: 285–320PubMedCrossRefGoogle Scholar
  18. Fujita T, Inoue T, Ogawa K, Iida K, Tamura N (1987) The mechanism of action of decay-accelerating factor (DAF). DAF inhibits the assembly of C3 convertases by dissociating C2a and Bb. J Exp Med 167: 1221–1228CrossRefGoogle Scholar
  19. Hoffmann EM (1969a) Inhibition of complement by a substance isolated from human ery-throcytes. I. Extraction from human erythrocyte stromata. Immunochemistry 6: 391–403CrossRefGoogle Scholar
  20. Hoffmann EM (1969b) Inhibition of complement by a substance isolated from human ery-throcytes. II. Studies on the site and mechanism of action. Immunochemistry 6: 405–419PubMedCrossRefGoogle Scholar
  21. Holers VM, Cole JL, Lublin DM, Seya T, Atkinson JP (1985) Human C3b-and C4b-regulatory proteins: a new multi-gene family. Immunol Today 6: 188–192CrossRefGoogle Scholar
  22. Homans SW, Ferguson MAJ, Dwek RA, Rademacher TW, Anand R, Williams AF (1988) Complete structure of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein. Nature 333: 269–272PubMedCrossRefGoogle Scholar
  23. Horstmann RD, Müller-Eberhard HJ (1986) Demonstration of C3b receptor-like activity and of decay-accelerating factor-like activity on rabbit erythrocytes. Eur J Immunol 16:1069–1073PubMedCrossRefGoogle Scholar
  24. Hourcade D, Holers VM, Atkinson JP (1989) The regulators of complement activation (RCA) gene cluster. Adv Immunol 45: 381–416PubMedCrossRefGoogle Scholar
  25. Kinoshita T, Medof ME, Silber R, Nussenzweig V (1985) Distribution of decay-accelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal hemoglobinuria. J Exp Med 162: 75–92PubMedCrossRefGoogle Scholar
  26. Kinoshita T, Medof ME, Nussenzweig V (1986) Endogenous association of decay-accelerating factor (DAF) with C4b and C3b on cell membranes. J Immunol 136: 3390–3395PubMedGoogle Scholar
  27. Kinoshita T, Rosenfeld SI, Nussenzweig V (1987) A high m.w. form of decay-accelerating factor (DAF-2) exhibits size abnormalities in paroxysmal nocturnal hemoglobinuria erythrocytes. J Immunol 138: 2994–2998PubMedGoogle Scholar
  28. Lewis SM, Dacie JV (1965) Neutrophil (leucocyte) alkaline phosphatase in paroxysmal nocturnal haemoglobinuria. Br J Haematol 11: 549–556PubMedCrossRefGoogle Scholar
  29. Low MG, Saltiel AR (1988) Structural and functional roles of glycosyl-phosphatidylinositol in membranes. Science 239: 268–275PubMedCrossRefGoogle Scholar
  30. Lublin DM, Griffith R, Atkinson JP (1986a) Influence of glycosylation on allelic and cell-specific.r variation, receptor processing, and ligand binding of the human complement C3b/C4b receptor (CRI). J Biol Chem 261: 5736–5744PubMedGoogle Scholar
  31. Lublin DM, Krsek-Staples J, Pangburn MK, Atkinson JP (1986b) Biosynthesis and glycosylation of the human complement regulatory protein decay-accelerating factor. J Immunol 137: 1629–1635PubMedGoogle Scholar
  32. Lublin DM, Lemons RS, Le Beau MM, Holers VM, Tykocinski M, Medof ME, Atkinson JP (1987) The gene encoding decay-accelerating factor (DAF) is located in the complement-regulatory locus on the long arm of chromosome 1. J Exp Med 165: 1731–1736PubMedCrossRefGoogle Scholar
  33. Lublin DM, Liszewski MK, Post TW, Arce MA, Le Beau MM, Rebentisch MB, Lemons RS, Seya T, Atkinson JP (1988) Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP): evidence for inclusion in the multi-gene family of complement-regulatory proteins. J Exp Med 168: 181–194PubMedCrossRefGoogle Scholar
  34. Manthei U, Nickells MW, Barnes SH, Ballard LL, Cui W, Atkinson JP (1988) Identification of a C3b/iC3 binding protein of rabbit platelets and leukocytes: a CR1-like candidate for the immune adherence receptor. J Immunol 140: 1228–1235PubMedGoogle Scholar
  35. McNearney T, Ballard L, Seya T, and Atkinson JP (1989) Membrane cofactor protein of complement is present on human fibroblast, epithelial and endothelial cells. J Clin Invest 84: 538–545PubMedCrossRefGoogle Scholar
  36. Medof ME, Kinoshita T, Nussenzweig V (1984) Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. J Exp Med 160: 1558–1578PubMedCrossRefGoogle Scholar
  37. Medof ME, Kinoshita T, Silber R, Nussenzweig V (1985) Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor. Proc Natl Acad Sci USA 82: 2980–2984PubMedCrossRefGoogle Scholar
  38. Medof ME, Walter EI, Roberts WL, Haas R, Rosenberry TL (2986) Decay accelerating factor of complement is anchored to cells by a C-terminal glycolipid. Biochemistry 25:6740–6747CrossRefGoogle Scholar
  39. Medof ME, Lublin DM, Holers VM, Ayers DJ, Getty RR, Leykam JF, Atkinson JP, Tykocinski ML (1987a) Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement. Proc Natl Acad Sci USA 84:2007–2011PubMedCrossRefGoogle Scholar
  40. Medof ME, Walter EI, Rutgers JL, Knowles DM, Nussenzweig V (1987b) Identification of the complement decay-accelerating factor (DAF) on epithelium and glandular cells and in body fluids. J Exp Med 165: 848–864PubMedCrossRefGoogle Scholar
  41. Moore JG, Frank MM, Müller-Eberhard HJ, Young NS (1985) Decay-accelerating factor is present on paroxysmal nocturnal hemoglobinuria erythroid progenitors and lost during erythropoiesis in vitro. J Exp Med 162: 1182–1192PubMedCrossRefGoogle Scholar
  42. Nicholson-Weller A, Bürge J, Austen KF (1981) Purification from guinea pig erythrocyte stroma of a decay-accelerating factor for the classical C3 convertase, C4b,2a. J Immunol 127: 2035–2039PubMedGoogle Scholar
  43. Nicholson-Weiler A, Bürge J, Fearon DT, Weller PF, Austen KF (1982) Isolation of a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3 convertases of the complement system. J Immunol 129: 184–189Google Scholar
  44. Nicholson-Weiler A, March JP, Rosenfeld SI, Austen KF (1983) Affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria are deficient in the complement regulatory protein decay-accelerating factor. Proc Natl Acad Sci USA 80: 5066–5070CrossRefGoogle Scholar
  45. Nicholson-Weiler A, March JP, Rosen CE, Spicer DB, Austen KF (1985a) Surface membrane expression by human blood leukocytes and platelets of decay-accelerating factor, a regulatory protein of the complement system. Blood 65: 1237–1244Google Scholar
  46. Nicholson-Weiler A, Spicer DB, Austen KF (1985b) Deficiency of the complement regulatory protein, “decay-accelerating factor”, on membranes of granulocytes, monocytes, and platelets in paroxysmal nocturnal hemoglobinuria. N Engl J Med 312: 1091–1097CrossRefGoogle Scholar
  47. Nicholson-Weiler A, Russian DA, Austen KF (1986) Natural killer cells are deficient in the surface expression of the complement regulatory protein, decay-accelerating factor (DAF). J Immunol 137: 1275–1279Google Scholar
  48. Pangburn MK (1986) Differences between the binding sites of the complement regulatory proteins DAF, CR1, and factor H on C3 convertases. J Immunol 136: 2216–2221PubMedGoogle Scholar
  49. Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1983) Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Proc Natl Sci USA 80: 5430–5434CrossRefGoogle Scholar
  50. Post TW, Atkinson JP (1989) The structure and organization of the MCP gene. FASEB J 3: A368Google Scholar
  51. Post TW, Arce MA, Liszewski MK, Atkinson JP, Lublin DM (1989) Structure of human DAF gene. FASEB J 3: A798Google Scholar
  52. Rey-Campos J, Rubinstein P, Rodriguez-de-Cordoba S (1987) Decay-accelerating factor. Genetic polymorphism and linkage to the RCA (regulator of complement activation) gene cluster in humans. J Exp Med 166: 246–252PubMedCrossRefGoogle Scholar
  53. Rey-Campos J, Rubinstein P, De Cordoba SR (1988) A physical map of the human regulator of complement activation gene cluster linking the complement genes CRI, CR2, DAF, and C4BP. J Exp Med 167: 664–669PubMedCrossRefGoogle Scholar
  54. Roberts WL, Santikarn S, Reinhold VN, Myher JJ, Kuksis A, Rosenberry TL (1988) Variations in the structure of glycoinositol phospholipids covalently attached to protein C-termini. FASEB J 2: A988Google Scholar
  55. Rosse WF, Parker CJ (1985) Paroxysmal nocturnal haemoglobinuria. Clin Haematol 14: 105–125PubMedGoogle Scholar
  56. Selvaraj P, Dustin ML, Silber R, Low MG, Springer TA (1987) Deficiency of lymphocyte function-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. J Exp Med 166: 1011–1025PubMedCrossRefGoogle Scholar
  57. Selvaraj P, Rosse WF, Silber R, Springer TA (1988) The major Fc receptor in blood has a phosphatidyl-inositol anchor and is deficient in paroxysmal nocturnal haemoglobinuria. Nature 333: 565–567PubMedCrossRefGoogle Scholar
  58. Seya T, Atkinson JP (1989) Characterization of the functional activity of membrane cofactor protein (MCP) of complement. Biochem J (in press)Google Scholar
  59. Seya T, Turner J, Atkinson JP (1986) Purification and characterization of a membrane protein (gp45-70) which is a cofactor for cleavage of C3b and C4b. J Exp Med 163: 837–855PubMedCrossRefGoogle Scholar
  60. Seya T, Farries T, Nickells M, Atkinson JP (1987) Additional forms of human decay-accelerating factor (DAF). J Immunol 139: 1260–1267PubMedGoogle Scholar
  61. Seya T, Ballard L, Bora N, McNearney T, Atkinson JP (1988) Distribution of membrane cofactor protein (MCP) of complement on human peripheral blood cells. Eur J Immunol 18:1289–1294PubMedCrossRefGoogle Scholar
  62. Schneider RJ, Kulczycki A, Law SK, Atkinson JP (1981) Isolation of a biologically active macrophage receptor for the third component of complement. Nature 290: 789–792PubMedCrossRefGoogle Scholar
  63. Stafford HA, Tykocinski ML, Lublin DM, Holers VM, Rosse WF, Atkinson JP, Medof ME (1988) Normal polymorphic variations and transcription of the decay-accelerating factor gene in paroxysmal nocturnal hemoglobinuria cells. Proc Natl Acad Sci USA 85: 880–884PubMedCrossRefGoogle Scholar
  64. Sugita Y, Uzawa M, Tomita M (1987) Isolation of decay-accelerating factor (DAF) from rabbit erythrocyte membranes. J Immunol Methods 104: 123–130PubMedCrossRefGoogle Scholar
  65. Telen MJ, Hall SE, Green AM, Moulds JJ, Rosse WF (1988) Identification of human erythrocyte blood group antigens on decay-accelerating factor (DAF) and an erythrocyte phenotype negative for DAF. J Exp Med 167: 1993–1998PubMedCrossRefGoogle Scholar
  66. Tse AGD, Barclay AN, Watts A, Williams AF (1985) A glycophospholipid tail at the carboxyl terminus of the Thy-1 glycoprotein of neurons and thymocytes. Science 230: 1003–1008PubMedCrossRefGoogle Scholar
  67. Turner JR (1984) Structural and functional studies of the C3b and C4b binding proteins of a human monocyte-like cell line (U937). Masters thesis, Washington University, St LouisGoogle Scholar
  68. Tykocinski ML, Shu HK, Ayers DJ, Walter El, Getty RR, Groger RK, Hauer CA, Medof ME (1988) Glycolipid reanchoring of T-lymphocyte surface antigen CD8 using the 3′ end sequence of decay-accelerating factor’s mRNA. Proc Natl Acad Sci USA 85: 3555–3559PubMedCrossRefGoogle Scholar
  69. Walter EI, Roberts WF, Rosenberry TL, Medof ME (1987) Analysis of fatty acids and inositol in the membrane anchor of human erythrocyte decay accelerating factor (DAF) (Abstract). Fed Proc 46: 772Google Scholar
  70. Wong WM, Fearon DT (1985) A C3b-binding protein on murine cells that shares antigenic determinants with the human C3b receptor (CR1) and is distinct from immune C3b receptors. J Immunol 134: 4048–4056PubMedGoogle Scholar
  71. Yu G, Holers VM, Seya T, Ballard L, Atkinson JP (1986) Identification of a third component of complement-binding glycoprotein of human platelets. J Clin Invest 78: 494–501PubMedCrossRefGoogle Scholar
  72. Zalman LS, Wood LM, Frank MM, Müller-Eberhard HJ (1987) Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria. J Exp Med 165: 572–577PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • D. M. Lublin
    • 1
  • J. P. Atkinson
    • 2
  1. 1.Division of Laboratory Medicine, Departments of Pathology and MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Division of Rheumatology, Department of Medicine, and Howard Hughes Medical Institute LaboratoriesWashington University School of MedicineSt. LouisUSA

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