Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

CFP (Complement Factor Properdin)

  • Anne M. Dersch
  • Eduardo Lamas-Basulto
  • Claudio Cortes
Reference work entry
First Online:
DOI: https://doi.org/10.1007/978-3-319-67199-4_101783
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Synonyms

 Factor P;  Properdin;  PFC (properdin factor complement);  PFD (P factor deficiency)

Historical Background

Complement was first described more than 100 years ago, and since then, findings and controversies have arisen that resulted in the discovery of the components that participate in each pathway of the complement system (alternative, classical, and lectin). It was widely accepted during the 1950s that microbial targets could only be lysed by a mixture of heat-sensitive components of human serum and antibodies, which we now know as the classical pathway (CP). During the same time, the first evidences of an “alternative” pathway capable of activating the complement system on targets without the presence of antibodies emerged. In 1954, Louis Pillemer and collaborators proposed that properdin acted as an initiator of alternative pathway (AP) activity, becoming what was called the “properdin system” (Pillemer et al. 1954). The discovery of this molecule was a major...

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References

  1. Agarwal S, Ferreira VP, Cortes C, Pangburn MK, Rice PA, Ram S. An evaluation of the role of properdin in alternative pathway activation on Neisseria meningitidis and Neisseria gonorrhoeae. J Immunol. 2010;185:507–16.PubMedPubMedCentralGoogle Scholar
  2. Agarwal S, Specht CA, Haibin H, Ostroff GR, Ram S, Rice PA, Levitz SM. Linkage specificity and role of properdin in activation of the alternative complement pathway by fungal glycans. MBio. 2011;2(5):e00178-11.Google Scholar
  3. Ali YM, Hayat A, Saeed BM, Haleem KS, Alshamrani S, Kenawy HI, Ferreira VP, Saggu G, Buchberger A, Lachmann PJ, Sim RB, Goundis D, Andrew PW, Lynch NJ, Schwaeble WJ. Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection. Proc Natl Acad Sci USA. 2014;111(14):5301–6.PubMedPubMedCentralGoogle Scholar
  4. Blatt AZ, Pathan S, Ferreira VP. Properdin: a tightly regulated critical inflammatory modulator. Immunol Rev. 2016a;274(1):172–90.PubMedPubMedCentralGoogle Scholar
  5. Blatt AZ, Saggu G, Kulkarni KV, Cortes C, Thurman JM, Ricklin D, Lambris JD, Valenzuela JG, Ferreira VP. Properdin-mediated C5a production enhances stable binding of platelets to granulocytes in human whole blood. J Immunol. 2016b;196(11):4671–80.PubMedPubMedCentralGoogle Scholar
  6. Cortes C, Ohtola JA, Saggu G, Ferreira VP. Local release of properdin in the cellular microenvironment: role in pattern recognition and amplification of the alternative pathway of complement. Front Immunol. 2013 Jan 17;3:412.PubMedPubMedCentralGoogle Scholar
  7. Fearon DT, Austen KF. Properdin: binding to C3b and stabilization of the C3b dependent C3 convertase. J Exp Med. 1975;142:856–63.PubMedGoogle Scholar
  8. Gulati S, Agarwal S, Vasudhev S, Rice PA, Ram S. Properdin is critical for antibody-dependent bactericidal activity against Neisseria gonorrhoeae that recruit C4b binding protein. J Immunol. 2012;188:3416–25.PubMedPubMedCentralGoogle Scholar
  9. Hamad OA, Mitroulis I, Fromell K, Kozarcanin H, Chavakis T, Ricklin D, Lambris JD, Ekdahl KN, Nilsson B. Contact activation of C3 enables tethering between activated platelets and polymorphonuclear leukocytes via CD11b/CD18. Thromb Haemost. 2015;114:1207–17.PubMedPubMedCentralGoogle Scholar
  10. Hourcade DE. The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem. 2006;281:2128–32.PubMedGoogle Scholar
  11. Ivanovska ND, Dimitrova PA, Luckett JC, El-Rachkidy Lonnen R, Schwaeble WJ, Stover CM. Properdin deficiency in murine models of nonseptic shock. J Immunol. 2008;180:6962–9.PubMedGoogle Scholar
  12. Jain U, Midgen CA, Schwaeble WJ, Stover CM, Stadnyk AW. Properdin Regulation of Complement Activation Affects Colitis in Interleukin 10 Gene-Deficient Mice. Inflamm Bowel Dis. 2015a;21:1519–28.PubMedGoogle Scholar
  13. Jain U, Cao Q, Thomas NA, Woodruff TM, Schwaeble WJ, Stover CM, Stadnyk AW. Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner. J Immunol. 2015b;194:3414–21.PubMedGoogle Scholar
  14. Jelezarova E, Vogt A, Lutz HU. Interaction of C3b(2)--IgG complexes with complement proteins properdin, factor B and factor H: implications for amplification. Biochem J. 2000;349:217–23.PubMedPubMedCentralGoogle Scholar
  15. Kimura Y, Miwa T, Zhou L, Song WC. Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement. Blood. 2008;15;111(2):732–40.Google Scholar
  16. Kimura Y, Zhou L, Miwa T, Song W-C. Genetic and therapeutic targeting of properdin in mice prevents complement-mediated tissue injury. J Clin Invest. 2010;120(10):3545–54.PubMedPubMedCentralGoogle Scholar
  17. Lesher AM, Nilsson B, Song WC. Properdin in complement activation and tissue injury. Mol Immunol. 2013;56:191–8.PubMedPubMedCentralGoogle Scholar
  18. Miwa T, Sato S, Gullipalli D, Nangaku M, Song WC. Blocking properdin, the alternative pathway, and anaphylatoxin receptors ameliorates renal ischemia-reperfusion injury in decay-accelerating factor and CD59 double-knockout mice. J Immunol. 2013; 190:3552–9.PubMedPubMedCentralGoogle Scholar
  19. Pangburn MK. Analysis of the natural polymeric forms of human properdin and their functions in complement activation. J Immunol. 1989;142:202–7.PubMedPubMedCentralGoogle Scholar
  20. Pillemer L, Blum L, Lepow IH, Ross OA, Todd EW, Wardlaw AC. The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena. Science. 1954;120:279–85.PubMedGoogle Scholar
  21. Ruseva MM, Vernon KA, Lesher AM, Schwaeble WJ, Ali YM, Botto M, Cook T, Song W, Stover CM, Pickering MC. Loss of properdin exacerbates C3 glomerulopathy resulting from factor H deficiency. J Am Soc Nephrol. 2013;24:43–52.PubMedGoogle Scholar
  22. Saggu G, Cortes C, Emch HN, Ramirez G, Worth RG, Ferreira VP. Identification of a novel mode of complement activation on stimulated platelets mediated by properdin. Immunobiology. 2012;217:1175–6.Google Scholar
  23. Schreiber RD, Medicus RG, Gotze O, Muller-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;142:760–72.PubMedGoogle Scholar
  24. Spitzer D, Mitchell LM, Atkinson JP, Hourcade DK. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J Immunol. 2007;179:2600–8.PubMedGoogle Scholar
  25. Stover CM, Luckett JC, Echtenacher B, Dupont A, Figgitt SE, Brown J, Männel DN, Schwaeble WJ. Properdin plays a protective role in polymicrobial septic peritonitis. J Immunol. 2008;180:3313–8.PubMedGoogle Scholar
  26. Vuagnat BB, Mach J, Le Doussal JM. Activation of the alternative pathway of human complement by autologous cells expressing transmembrane recombinant properdin. Mol Immunol. 2000;37:467–78.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Anne M. Dersch
    • 1
  • Eduardo Lamas-Basulto
    • 1
  • Claudio Cortes
    • 1
  1. 1.Oakland University William Beaumont School of MedicineRochesterUSA