Ancient Origin of the Complement System: Emerging Invertebrate Models

  • Maria Rosaria Pinto
  • Daniela Melillo
  • Stefano Giacomelli
  • Georgia Sfyroera
  • John D. Lambris
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 598)


Complement System Complement Component Horseshoe Crab Ancient Origin Coelomic Fluid 
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. Al-Sharif, W.Z., Sunyer, J.O., Lambris, J.D. and Smith, L.C. (1998) Sea urchin coelomocytes specifically express a homologue of the complement component C3. J. Immunol. 160, 2983-2997.PubMedGoogle Scholar
  2. Andersson Nordahl, E., Rydengård, V., Nyberg, P., Nitsche, D.P., Mörgelin, M., Malmsten, M., Björck, L. and Schmidtchen, A. 2004 Activation of the complement system generates antibacterial peptides. Proc. Natl. Acad. Sci. USA 101, 16879-16884.CrossRefGoogle Scholar
  3. Azumi, K., De Santis, R., De Tomaso, A., Rigoutsos, I., Yoshizaki, F., Pinto, M.R., Marino, R., Shida, K., Ikeda, M., Ikeda, M., Arai, M., Inoue, Y., Shimizu, T., Satoh, N., Rokhsar, D.S., Du Pasquier, L., Kasahara, M., Satake, M., and Nonaka, M. (2003). Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: “waiting for Godot”. Immunogenetics 55, 570-581.PubMedCrossRefGoogle Scholar
  4. Bertheussen, K. (1982) Receptors for complement on echinoid phagocytes. II. Purified human complement mediates echinoid phagocytosis. Dev. Comp. Immunol. 6, 635-642.PubMedGoogle Scholar
  5. Bertheussen, K. and Seljelid R. (1982) Receptors for complement on echinoid phagocytes. I. The opsonic effect of vertebrate sera on echinoid phagocytosis. Dev. Comp. Immunol. 6, 423-431.PubMedGoogle Scholar
  6. Bertheussen, K. (1983) Complement-like activity in sea urchin coelomic fluid. Dev. Comp. Immunol. 7, 21-31.PubMedCrossRefGoogle Scholar
  7. Clow, L.A., Gross, P.S., Shih, C-S. and Smith, L.C. (2000) Expression of SpC3, the sea urchin complement component, in response to lipopolysaccharide. Immunogenetics 51, 1021-1033.PubMedCrossRefGoogle Scholar
  8. Clow, L.A., Raftos, D.A., Gross, P.S. and Smith, L.C. (2004) The sea urchin complement homologue, SpC3, functions as an opsonin. J. Exp. Biol. 207, 2147-2155.PubMedCrossRefGoogle Scholar
  9. Dehal P., Satou, Y., Campbell, R.K., Chapman, J., Degnan, B., De Tomaso, A. Davidson, B., Di Gregorio, A., Gelpke, M., Goodstein D.M. et al. 2002. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298, 2157-2167.PubMedCrossRefGoogle Scholar
  10. Delsuc, F., Brinkmann, H., Chourrout, D. and Philippe, H. (2006) Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature 439, 965-968. Edds, K. (1993) Cell biology of echinoid coelomocytes. I Diversity and characterization of cell types. J. Invert. Pathol. 61, 173-178.PubMedCrossRefGoogle Scholar
  11. Dishaw, L.J., Smith, S.L. and Bigger, C.H. 2005 Characterization of a C3-like cDNA in a coral: phylogenetic implications. Immunogenetics 57, 535-548.PubMedCrossRefGoogle Scholar
  12. Ember, J.A., Jagels, M.A. and Hugli, T.E. (1998) . Characterization of complement anaphylatoxins and their biological responses. In: J.E. Volanakis and M.M. Frank, (Eds.) The Human Complement System in Health and Disease. Marcel Dekker, New York, pp. 241-284.Google Scholar
  13. Endo, Y., Nonaka, M., Saiga, H., Kakinuma, Y., Matsushita, A., Takahashi, M., Matsushita, M. and Fujita, T. (2003) Origin of mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 involved in the lectin complement pathway traced back to the invertebrate, amphioxus. J Immunol. 170, 4701-4707.PubMedGoogle Scholar
  14. Fujita, T. (2002) Evolution of the lectin-complement pathway and its role in innate immunity. Nat. Rev. Immunol. 2, 346-353.PubMedCrossRefGoogle Scholar
  15. Gross, P.S., Clow, L.A. and Smith, L.C. (2000) SpC3, the complement homologue from the purple sea urchin, Strongylocentrotus purpuratus, is expressed in two subpopulations of the phagocytic coelomocytes. Immunogenetics 51, 1034-1044.PubMedCrossRefGoogle Scholar
  16. Ji, X, Azumi, K, Sasaki, M. and Nonaka M. (1997) Ancient origin of the complement lectin pathway revealed by molecular cloning of mannan binding protein-associated serine protease from a urochordate, the Japanese ascidian, Halocynthia roretzi. Proc. Natl. Acad. Sci. USA 94, 6340-6345.PubMedCrossRefGoogle Scholar
  17. Johnson, P.T. (1969) The coelomic elements of sea urchins (Strongylocentrotus). I. The normal coelomocytes; their morphology and dynamics in hanging drops. J. Invert. Pathol. 13, 25-41.CrossRefGoogle Scholar
  18. Kairies, N., Beisel, H.G., Fuentes-Prior, P., Tsuda, R., Muta, T., Iwanaga, S., Bode, W., Huber, R. and Kawabata, S. (2001) The 2.0-A crystal structure of tachylectin 5A provides evidence for the common origin of the innate immunity and the blood coagulation systems. Proc. Natl. Acad. Sci. U S A 98, 13519-13524.Google Scholar
  19. Kang, Y-S., Do, Y., Lee, H-K., Park, S.H., Cheong, C., Lynch, R.M., Loeffler, J.M., Steinman, R.M. and Park, C.G. 2006 A dominant complement fixation pathway for pneumococcal polysaccharides initiated by SIGN-R1 interacting with C1q. Cell 125, 47-58.PubMedCrossRefGoogle Scholar
  20. Karp, D.R., Parker, K.L., Shreffler, D.C. and Capra, J.D. (1981) Characterization of the murine C4 precursor (pro-C4): evidence that the carboxyterminal subunit is the C4 gamma-chain. J. Immunol. 126, 2060-2061.PubMedGoogle Scholar
  21. Kelly, K.L., Cooper, E.L. and Raftos, D.A. (1992) Purification and characterization of a humoral opsonin from the solitary urochordate Styela clava. Comp. Biochem. Physiol. 103B, 749-753.Google Scholar
  22. Kenjo, a., Takahashi, M., Matsushita, M., Endo, Y., Nkata, M., Mizuochi, T. and Fujita, T. (2001) Cloning and characterization of novel ficolins from the solitary ascidian, Halocynthia roretzi. J. Biol. Chem.276, 19959-19965.PubMedCrossRefGoogle Scholar
  23. Kraut, J. (1977) Serine proteases: structure and mechanism of catalysis. Annu. Rev. Biochem. 46, 331-358.PubMedCrossRefGoogle Scholar
  24. Lambris, J.D. (1990) The Third Component of Complement - Chemistry and Biology. Springer-Verlag, Heidelberg.Google Scholar
  25. Marino R., Kimura, Y., De Santis, R., Lambris, J.D. and Pinto M.R. (2002). Complement in urochordates: cloning and characterization of two C3-like genes in the ascidian Ciona intestinalis. Immunogenetics 53, 1055-1064.PubMedCrossRefGoogle Scholar
  26. Mastellos, D. and Lambris, J.D. (2002) Complement: more than a ‘guard’ against invading pathogens? Trends Immunol. 23, 485-91.PubMedCrossRefGoogle Scholar
  27. Matsushita, M., Endo, Y., Nonaka, M. and Fujita, T. (1998) Complement-related serine proteases in tunicates and vertebrates. Curr. Opin. Immunol. 10, 29-35.PubMedCrossRefGoogle Scholar
  28. Matsushita, M., Endo, Y. and Fujita, T. (2000) Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease. J. Immunol. 164, 2281-2284.PubMedGoogle Scholar
  29. Matsushita, M. and Fujita, T. (2002) The role of ficolins in innate immunity. Immunobiology 205, 490-497.PubMedCrossRefGoogle Scholar
  30. Matsushita, M., Matsushita, A., Endo, Y., Nakata, M., Kojima, N., Mizuochi, T. and Fujita, T. (2004) Origin of the classical complement pathway: lamprey orthologue of mammalian C1q acts as a lectin. Proc. Natl. Acad. Sci. USA 101, 10127-10131.PubMedCrossRefGoogle Scholar
  31. Melillo, D., Sfyroera, G., De Santis, R., Graziano, R., Marino, R., Lambris, J.D. and Pinto, M.R. (2006) First identification of a chemotactic receptor in an invertebrate species: structural and functional characterization of Ciona intestinalis C3a Receptor. J. Immunol. 177, 4132-4140.PubMedGoogle Scholar
  32. Miyazawa, S., Azumi, K., and Nonaka, M. (2001) Cloning and characterization of integrin α subunits from the solitary ascidian, Halocynthia roretzi. J. Immunol. 166, 1710-1715.PubMedGoogle Scholar
  33. Miyazawa, S. and Nonaka, M. (2004) Characterization of novel ascidian β integrins as primitive complement receptor subunits. Immunogenetics 55, 836-844.Google Scholar
  34. Multerer, K.A. and Smith, L.C. (2004) Two cDNAs from the purple sea urchin, Strongylocentrotus purpuratus, encoding mosaic proteins with domains found in factor H, factorI, and complement components C6 and C7. Immunogenetics 56, 89-106.PubMedCrossRefGoogle Scholar
  35. Nonaka, M. (1994) Molecular analysis of the lamprey complement system. Fish Shellfish Immunol. 4, 437-446.CrossRefGoogle Scholar
  36. Nonaka, M., Azumi, K., Ji, X., Namikawa-Yamada, C., Sasaki, M., Saiga, H., Dodds, A.W., Sekine, H., Homma, M.K., Matsushita, M., Endo, Y. and Fujita, T. (1999) Opsonic complement component C3 in the solitary ascidian, Halocynthia roretzi. J. Immunol. 162, 387-391.PubMedGoogle Scholar
  37. Nonaka, M. and Kimura, A. (2006) Genomic view of the evolution of the complement system. Immunogenetics 58, 701-713.PubMedCrossRefGoogle Scholar
  38. Pearce, S., Newton, R.A., Nair, S.V. and Raftos, D.A. (2001) Humoral opsonins of the tunicate, Pyura stolonifera. Dev. Comp. Immunol. 25, 377-385.PubMedCrossRefGoogle Scholar
  39. Pinto M.R., Chinnici, C.M., Kimura, Y., Melillo, D., Marino, R., Spruce, L.A., De Santis, R., Parrinello, N. and Lambris, J. D. (2003) CiC3-1a-mediated chemotaxis in the deuterostome invertebrate Ciona intestinalis (Urochordata). J Immunol. 171, 5521-5528.PubMedGoogle Scholar
  40. Raftos, D.A., Nair, S. V., Robbins, J., Newton, R. A. and Peters. R. (2002) A complement component C3-like protein from the tunicate, Styela plicata. Dev. Comp. Immunol. 26, 307-312.PubMedCrossRefGoogle Scholar
  41. Raftos, D.A., Robbins, J. Newton, R.A. and Nair, S. V. (2003) A complement component C3a-like peptide stimulates chemotaxis by hemocytes from an invertebrate chordate-the tunicate, Pyura stolonifera. Comp. Biochem. Physiol. Part A 134, 377-386.CrossRefGoogle Scholar
  42. Raftos D.A., Stillman, D.L. and Cooper, E. L. (1998) Chemotactic responses of tunicate (Urochordata, Ascidiacea) hemocytes in vitro. J. Invertebr. Pathol. 72, 44-49.PubMedCrossRefGoogle Scholar
  43. Sekine, H., Kenjo, A., Azumi, K., Ohi, G., Takahashi, M., Kasukawa, R., Ichikawa, N., Nakata, M., Mizuochi, T., Matsushita M., Endo, Y. and Fujita, T. (2001) An ancient lectin-dependent complement system in an ascidian: novel lectin isolated from the plasma of the solitary ascidian, Halocynthia roretzi. J. Immunol. 167, 4504-4510.PubMedGoogle Scholar
  44. Shah, M., Brown, K.M. and Smith, L.C. (2003) The gene encoding the sea urchin complement protein, SpC3, is expressed in embryos and can be upregulated by bacteria. Dev. Comp. Immunol. 27, 529-538.PubMedCrossRefGoogle Scholar
  45. Smith, L.C. (2002) Thioester function is conserved in SpC3, the sea urchin homologue of the complement component C3. Dev. Comp. Immunol. 26, 603-614.PubMedCrossRefGoogle Scholar
  46. Smith, L.C., Britten, R.J. and Davidson E.H. (1995) Lipopolysaccharide activates the sea urchin immune system. Dev. Comp. Immunol. 19, 217-224.PubMedCrossRefGoogle Scholar
  47. Smith, L.C., Chang, L., Britten, R.J. and Davidson, E.H. (1996) Sea urchin genes expressed in activated coelomocytes are identified by expressed sequence tags. J. Immunol. 156, 593-602.PubMedGoogle Scholar
  48. Smith, L.C., Clow, L.A. and Terwilliger, D.P. (2001) The ancestral complement system in sea urchins. Immunol. Rev. 180, 16-34.PubMedCrossRefGoogle Scholar
  49. Smith, L.C., Shih, C-S. and Dachenhausen, S.G. (1998) Coelomocytes express SpBf, a homologue of factor B, the second component in the sea urchin complement system. J. Immunol. 161, 6784-6793.PubMedGoogle Scholar
  50. Song, W-C., Sarrias, M.R. and Lambris, J.D. (2000) Complement and innate immunity. Immunopharmacology 49, 187-198.PubMedCrossRefGoogle Scholar
  51. Suzuki, M.M., Satoh, N. and Nonaka, M. (2002) C6-like and C3-like molecules from the cephalochordate amphioxus, suggest a cytolytic complement system in invertebrates. J. Mol. Evol. 54, 671-679.PubMedCrossRefGoogle Scholar
  52. Vienne, A. and Pontarotti, P. (2006) Metaphylogeny of 82 gene families sheds a new light on chordate evolution.Int. J. Biol. Sci. 2, 32-37.Google Scholar
  53. Vogel, C.W., Bredehorst, R., Fritzinger, D.C., Grunwald, T., Ziegelmuller, P. and Kock, M.A. (1996) Structure and function of cobra venom factor, the complement-activating protein in cobra venom. Adv. Exp. Med. Biol. 391, 97-114.PubMedGoogle Scholar
  54. Wetsel, R.A., Kildsgaard, J. and Haviland, D.L. (2000) Complement anaphylatoxins (C3a, C4a, C5a) and their receptors (C3aR, C5aR/CD88) as therapeutic targets in inflammation. In: J.D. Lambris and V.M. Holers, (Eds.), Therapeutics Interventions in the Complement System. The Humana Press, New York, pp. 113-153.CrossRefGoogle Scholar
  55. Yoshizaki, F.Y., Ikawa, S., Satake, M, Satoh, N., Nonaka, M. (2005) Structure and the evolutionary implication of the triplicated complement factor B genes of a urochordate ascidian, Ciona intestinalis. Immunogenetics 56, 930-942.PubMedCrossRefGoogle Scholar
  56. Zhu, Y., Thangamani, S., Ho, B. and Ding, J.L. (2005) The ancient origin of the complement system. EMBO J. 24, 382-394.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Maria Rosaria Pinto
    • 1
  • Daniela Melillo
    • 1
  • Stefano Giacomelli
    • 1
  • Georgia Sfyroera
    • 2
  • John D. Lambris
    • 2
  1. 1.Laboratory of Cell BiologyStazione Zoologica “Anton Dohrn”NapoliItaly
  2. 2.Department of Pathology and Laboratory MedicineUniversity of PennsylvaniaPhiladelphia

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