Skip to main content
Log in

Properdin: Approaching four decades of research

  • The Year in Complement
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Properdin plays a key role in the alternative pathway by stabilizing the C3 convertase. This review chronicles the evolution of our knowledge of the structure and function of properdin over the 40 years since its discovery. The story begins with the first description of properdin and the controversy that ensued over its existence. Then, this review describes: the rediscovery and acceptance of properdin and the alternative pathway as important components of natural immunity; properdin structure and molecular sequence; speculations on the significance of sequence similarities to thrombospondin and other proteins, and properdin biosynthesis. Finally, this review characterizes properdin deficiency. Properdin does indeed appear to play an important role in homeostasis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Pillemer L, Blum L, Lepow IH, Ross OA, Todd EW, Wardlaw AC: The properdin system and immunity: Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena. Science 1954;120:279–285.

    Article  PubMed  CAS  Google Scholar 

  2. Fearon DT, Austen KF: Properdin: Binding to C3b and stabilization of the C3b-dependent C3 convertase. J Exp Med 1975;142:856–863.

    Article  PubMed  CAS  Google Scholar 

  3. Sjöholm AG, Braconier JH, Söderström C: Properdin deficiency in a family with fulminant meningococcal infections. Clin Exp Immunol 1982;50:291–297.

    PubMed  Google Scholar 

  4. Densen P, Weiler JM, Griffiss JM, Hoffmann LG: Familial properdin deficiency and fatal meningococcemia. N Engl J Med 1987;316:922–926.

    PubMed  CAS  Google Scholar 

  5. Lepow IH: Louis Pillemer, properdin and scientific controversy. J Immunol 1980;125:471–478.

    PubMed  CAS  Google Scholar 

  6. Ratnoff WD: A war with the molecules: Louis Pillemer and the history of properdin. Perspect Biol Med 1980;23:638–657.

    PubMed  CAS  Google Scholar 

  7. Pillemer L, Ecker EE: Anticomplementary factor in fresh yeast. J Biol Chem 1941;137:139–142.

    CAS  Google Scholar 

  8. Pillemer L, Lepow IH, Blum L: The requirement for a hydrazine-sensitive serum factor and heat-labile serum factors in the inactivation of human C'3 by zymosan. J Immunol 1953;71:339–351.

    PubMed  CAS  Google Scholar 

  9. Pillemer L, Ecker EE, Oncley JL, Cohn EJ: The preparation and physicochemical characterization of the serum protein components of complement. J Exp Med 1941;74:297–308.

    Article  CAS  Google Scholar 

  10. Pillemer L, Toll D: The purification of diptherial toxoid. Science 1947; 105:102–103.

    Article  PubMed  CAS  Google Scholar 

  11. Pillemer L, Burrell JI, Ross OA: Separation and immunologic evaluation of soluble pertussal antigens. Science 1947;106:36–37.

    Article  PubMed  Google Scholar 

  12. Nelson RA: An alternative mechanism for the properdin system. J Exp Med 1958;108:515–535.

    Article  PubMed  CAS  Google Scholar 

  13. Lepow IH, Pillemer L, Schoenberg MD, Todd EW, Wedgwood RJ: The properdin system and immunity. X. Characterization of partially purified human properdin. J Immunol 1959;83:428–436.

    PubMed  CAS  Google Scholar 

  14. Pensky J, Wurz L, Pillermer L, Lepow IH: The properdin system and immunity. XII. Assay, properties and partial purification of hydrazine-sensitive serum factor (factor A) in the properdin system. Z Immunitätsforsch 1959;118:329–348.

    CAS  Google Scholar 

  15. Blum L, Pillemer L, Lepow IH: The properdin system and immunity. XIII. Assay and properties of a heatlabile serum factor (factor B) in the properdin system. Z Immunitätsforsch 1959;118:349–357.

    CAS  Google Scholar 

  16. Kabat EA, Mayer MM: Experimental Immunochemistry ed 2 (Springfield, Thomas, 1961).

    Google Scholar 

  17. Pensky J, Hinz CF, Todd EW, Wedgwood RJ, Boyer JT, Lepow IH: Properties of highly purified human properdin. J Immunol 1968; 100:142–158.

    CAS  Google Scholar 

  18. Sandberg AL, Oliveira B, Osler AG: Two complement interaction sites in guinea pig immunoglobulins. J Immunol 1971;106:282–285.

    PubMed  CAS  Google Scholar 

  19. Gewurz H, Shin HS, Mergenhagen SE: Interactions of the complement system with endotoxic lipopolysaccharide: Consumption of each of the six terminal complement components. J Exp Med 1968;128:1049–1057.

    Article  PubMed  CAS  Google Scholar 

  20. Sandberg AL, Osler AG, Shin HS, Oliveira B: The biologic activities of guinea pig antibodies. II. Modes of complement interaction with γ1 and γ2 immunoglobulins. J Immunol 1970;104:329–334.

    PubMed  CAS  Google Scholar 

  21. Reid KBM: Complement fixation by the F(ab′)2 fragment of pepsintreated rabbit antibody. Immunology 1971;20:649–658.

    PubMed  CAS  Google Scholar 

  22. Marcus RL, Shin HS, Mayer MM: An alternate complement pathway: C-3 cleaving activity, not due to C4,2a on endotoxic lipopolysaccharide after treatment with guinea pig serum, relation to properdin. Proc Natl Acad Sci USA 1971;68:1351–1354.

    Article  PubMed  CAS  Google Scholar 

  23. Müller-Eberhard HJ, Götze O: C3 proactivator convertase and its mode of action. J Exp Med 1972; 135:1003–1008.

    Article  PubMed  Google Scholar 

  24. Goodkofsky I, Stewart AH, Lepow IH: Relationship of C3 and factor A of the properdin system (abstract). J Immunol 1973;111:287.

    Google Scholar 

  25. Götze O, Müller-Eberhard HJ: The C3-activator system: An alternate pathway of complement activation. J Exp Med 1971;134:90s-108s.

    PubMed  Google Scholar 

  26. Alper CA, Goodkofsky I, Lepow IH: The relationship of glycine-rich β-glycoprotein to factor B in the properdin system and to the cobra factor-binding protein of human serum. J Exp Med 1973;137:424–437.

    Article  PubMed  CAS  Google Scholar 

  27. LeSavre PH, Müller-Eberhard HJ: Mechanisms of action of factor D of the alternative complement pathway. J Exp Med 1978;148:1498–1509.

    Article  PubMed  CAS  Google Scholar 

  28. Fearon DT, Austen KF, Ruddy S: Formation of a hemolytically active cellular intermediate by the interaction between properdin factors B and D and the activated third component of complement. J Exp Med 1973;138:1305–1313.

    Article  PubMed  CAS  Google Scholar 

  29. Fearon DT, Austen KF, Ruddy S: Properdin factor D, II. Activation to D by properdin. J Exp Med 1974; 140:426–436.

    Article  PubMed  CAS  Google Scholar 

  30. Fearon DT, Austen KF: Properdin: Initiation of alternative complement pathway. Proc Natl Acad Sci USA 1975;72:3220–3224.

    Article  PubMed  CAS  Google Scholar 

  31. Schrelber RD, Medicus RG, Götze O, Müller-Eberhard HJ: Properdin-and nephritic factor-dependent C3 convertases: Requirement of native C3 for enzyme formation and the function of bound C3b as properdin receptor. J Exp Med 1975;142:760–772.

    Article  Google Scholar 

  32. Weiler JM, Daha MR, Austen KF, Fearon DT: Control of the amplification convertase of complement by the plasma protein β1H. Proc Natl Acad Sci USA 1976;73:3268–3272.

    Article  PubMed  CAS  Google Scholar 

  33. Medicus RG, Götze O, Müller-Eberhard HJ: Afternative pathway of complement: Recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway. J Exp Med 1976;144:1076–1093.

    Article  PubMed  CAS  Google Scholar 

  34. Daha MR, Fearon DT, Austen KF: C3 requirements for formation of alternative pathwawy C5 convertase. J Immunol 1976;117:630–634.

    PubMed  CAS  Google Scholar 

  35. DiScipio RG: The binding of human complement proteins C5, factor B, β1H and preperdin to complement fragment C3b on zymosan. Biochem J 1981;199:485–496.

    PubMed  CAS  Google Scholar 

  36. Farries TC, Lachmann PJ, Harrison RA: Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products. Biochem J 1988;252:47–54.

    PubMed  CAS  Google Scholar 

  37. Lambris JD, Alsenz J, Schulz TF, Dierich MP: Mapping of the properdin-binding site in the third component of complement. Biochem J 1984; 217:323–326.

    PubMed  CAS  Google Scholar 

  38. Daoudaki ME, Becherer JD, Lambris JD: A 34-amino acid peptide of the third component of complement mediates properdin binding. J Immunol 1988; 140:1577–1580.

    PubMed  CAS  Google Scholar 

  39. Prins HK, Pondman KW: Preparation of properdin by ion-exchange resin adsorption. Proc 6th Congr Eur Soc Hematol, Copenhagen, 1957;S995–997.

  40. Chapitis J, Lepow IH: Multiple sedimenting species of properdin in human serum and interaction of purified properdin with the third component of complement. J Exp Med 1976;143:241–257.

    Article  PubMed  CAS  Google Scholar 

  41. Minta JO, Lepow IH: Studies on the sub-unit structure of human properdin. Immunochemistry 1974;11:361–368.

    Article  PubMed  CAS  Google Scholar 

  42. Minta JO, Kunar ES: Effect of proteolytic digestion on the structure and function of human properdin. J Immunol 1976;116:1099–1104.

    PubMed  CAS  Google Scholar 

  43. Reid KBM: Preparation of human properdin. Methods Enzymol 1981; 80:143–150.

    Article  CAS  Google Scholar 

  44. Götze O, Medicus R, Müller-Eberhard HJ: Alternative pathway of complement: Nonenzymatic, reversible transition of precursor to active properdin. J Immunol 1977; 118:525–528.

    PubMed  Google Scholar 

  45. DiScipio RG: Properdin is a trimer. Mol Immunol 1982;19:631–635.

    Article  PubMed  CAS  Google Scholar 

  46. Smith CA, Pangburn MK, Vogel CW, Müller-Eberhard HJ: Molecular architecture of human properdin, a positive regulator of the alternative pathway of complement. J Biol Chem 1984;259:4582–4588.

    PubMed  CAS  Google Scholar 

  47. Pangburn MK: Analysis of the natural polymeric forms of human properdin and their functions in compiement activation. J Immunol 1989; 142:202–207.

    PubMed  CAS  Google Scholar 

  48. Perkins SJ, Nealis AS, Haris PI, Chapman D, Goundis D, Reid KBM: Secondary structure in properdin of the complement cascade and related proteins: A study by Fourier transform infrared spectroscopy. Biochemistry 1989;28:7176–7182.

    Article  PubMed  CAS  Google Scholar 

  49. Adam C, Williams DG, Peters DK: Mechanisms of activation of the properdia system: Studies on properdin electrophoretic mobility in agarose activation of the alternative pathway. Clin Exp Immunol 1975; 22:240–248.

    PubMed  CAS  Google Scholar 

  50. Minta JO: Changes in the immunochemical properties of highly purified properdin in human serum. J Immunol 1975;114:1415–1421.

    PubMed  CAS  Google Scholar 

  51. Minta JO: Production of antiserum to human properdin and demonstration of antigenic differences between the native and activated protein. Proc Exp Biol Med 1976;151: 411–414.

    CAS  Google Scholar 

  52. Medicus RG, Esser AF, Fernandez HN, Müller-Eberhard HJ: Native and activated properdin: Interconvertibility and identity of amino-and carboxy-terminal sequences. J Immunol 1980;124:602–606.

    PubMed  CAS  Google Scholar 

  53. Farries TC, Finch JT, Lachmann PJ, Harrison RA: Resolution and analysis of ‘native’ and ‘activated’ properdin. Biochem J 1987;243:507–517.

    PubMed  CAS  Google Scholar 

  54. Reid KBM, Gagnon J: Amino acid sequence studies of human properdin—N-terminal sequence analysis and alignment of the fragments produced by limited proteolysis with trypsin and the peptides produced by cyanogen bromide treatment. Mol Immunol 1981;18:949–959.

    Article  PubMed  CAS  Google Scholar 

  55. Nakano Y, Matsuda T, Sakamoto T, Tomita M: Isolation and characterization of rabbit properdin of the alternative complement pathway. J Immunol Methods 1986;90:77–83.

    Article  PubMed  CAS  Google Scholar 

  56. Goundis D, Reid KBM: Properdin, the terminal complement components, thrombospondin and the circumsporozoite protain of malaria parasites contain similar sequence motifs. Nature 1988;335:82–85.

    Article  PubMed  CAS  Google Scholar 

  57. Robson KJH, Hall JRS, Jennings MW, Harris TJR, Marsh K, Newbold CI, Tate VE, Weatherall DJ: A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature 1988;335:79–82.

    Article  PubMed  CAS  Google Scholar 

  58. Reid KBM, Day AJ: Structure-function relationships of the complement components. Immunol Today 1989;10:177–180.

    Article  PubMed  CAS  Google Scholar 

  59. Prater CA, Plotkin J, Jaye D, Frazier WA: The properdin-like type I repeats of human thrombospondin contain a cell attachment site. J Cell Biol 1991;112:1031–1040.

    Article  PubMed  CAS  Google Scholar 

  60. Rich KA, George FW, Law JL, Martin WJ: Cell-adhesive motif in region II of malarial circumsporozoite protein. Science 1990;249:1574–1577.

    Article  PubMed  CAS  Google Scholar 

  61. Nolan KF, Schwaeble W, Kaluz S, Dierich MP, Reid KBM: Molecular cloning of the cDNA coding for properdin, a positive regulator of the alternative pathway of human complement. Eur J Immunol 1991;21: 771–776.

    Article  PubMed  CAS  Google Scholar 

  62. Maves KK, Weiler JM: Detection of properdin mRNA in human peripheral blood monocytes and spleen. J Lab Clin Med 1992;120:762–766.

    PubMed  CAS  Google Scholar 

  63. Maves KK, Moser DR, Densen P, Weiler JM: Comparison of properdin sequence in 3 species shows conservation of thrombospondin repeats (abstract). Complement Inflamm 1991;8:191–192.

    Google Scholar 

  64. Bentley C, Fries W, Brade V: Synthesis of factors D. B and P of the alternative pathway of complement activation as well as of C3, by guinea-pig peritoneal macrophages in vitro. Immunology 1978;35:971–980.

    PubMed  CAS  Google Scholar 

  65. Whaley K: Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes. J Exp Med 1980;151:501–516.

    Article  PubMed  CAS  Google Scholar 

  66. Minta JO: Biosynthesis of complement factor P (properdin) by the human pre-monocyte cell line (U937). Mol Immunol 1988;25:1363–1370.

    Article  PubMed  CAS  Google Scholar 

  67. Farries TC, Atkinson JP: Biosynthesis of properdin. J Immunol 1989; 142:842–847.

    PubMed  CAS  Google Scholar 

  68. Truedsson L, Sturfelt G, Offenbartl K, Sjöholm AG: The spleen is not a major synthetic site of alternative pathway components. Complement Inflamm 1990;7:52–56.

    PubMed  CAS  Google Scholar 

  69. Minta JO: Biosynthesis of properdin by U937 cells and Hep G2 cells (abstract). Fed Proc 1987;46:771.

    Google Scholar 

  70. De Ceulaer C, Papazoglou S, Whaley K: Increased biosynthesis of complement components by cultured monocytes, synovial fluid macrophages and synovial membrane cells from patients with rheumatoid arthritis. Immunology 1980;41:37–43.

    PubMed  Google Scholar 

  71. Figueroa JE, Densen P: Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 1991;4:359–395.

    PubMed  CAS  Google Scholar 

  72. Braconier JH, Sjöholm AG, Söderström C: Fulminant meningococcal infections in a family with inherited deficiency of properdin. Scand J Infect Dis 1983;15:339–345.

    PubMed  CAS  Google Scholar 

  73. Sjöholm AG, Söderström C, Nilsson LA: A second variant of properdin deficiency: The detection of properdin at low concentrations in affected males. Complement 1988;5:130–140

    PubMed  Google Scholar 

  74. Sjöholm AG, Nilsson LA: Properdin deficiency in a second Swedish family: Absence of clinical manifestations (abstract). Compiement 1985;2:73.

    Google Scholar 

  75. Goundis D, Holt SM, Boyd Y, Reid KBM: Localization of the properdin structural locus to Xp11.23-Xp21.1. Genomics 1989;5:56–60.

    Article  PubMed  CAS  Google Scholar 

  76. Coleman MP, Murray JC, Willard HF, Nolan KF, Reid KBM, Blake DJ, Lindsay S, Bhattacharya SS, Wright A, Davies KE: Genetic and physical mapping around the properdin P gene. Genomics 1991;11: 991–996.

    Article  PubMed  CAS  Google Scholar 

  77. Ecker EE: On Louis Pillemer. Z Immunitätsforsch 1959;118:225–227.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maves, K.K., Weiler, J.M. Properdin: Approaching four decades of research. Immunol Res 12, 233–243 (1993). https://doi.org/10.1007/BF02918255

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02918255

Key Words

Navigation