What is common between the classical lectin and alternative pathway of the complement system?

1. Walport MJ . Complement. First of two parts. N Engl J Med 2001; 344:1058–1066.

   Article  CAS  PubMed  Google Scholar 

2. Janeway CA Jr, Travers P, Walport M, Shlomchik M . Immunobiology: The Immune System in Health and Disease. 6th Edition. New York: Garland Publishing, 2005.

   Google Scholar 

3. Volanakis JE, Frank MM . The Human Complement System in Health and Disease. New York: Marcel Dekker Inc., 1998.

   Book  Google Scholar 

4. Jensen JA, Festa E, Smith DS, Cayer M . The complement system of the nurse shark: hemolytic and comparative characteristics. Science 1981; 214:566–569.

   Article  CAS  PubMed  Google Scholar 

5. Suzuki MM, Satoh N, Nonaka M . C6-like and C3-like molecules from the cephalochordate, amphioxus, suggest a cytolytic complement system in invertebrates. J Mol Evol 2002; 54:671–679.

   Article  CAS  PubMed  Google Scholar 

6. Azumi K, De Santis R, De Tomaso A, et al. Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: “waiting for Godot”. Immunogenetics 2003; 55:570–581.

   Article  CAS  PubMed  Google Scholar 

7. Al-Sharif WZ, Sunyer JO, Lambris JD, Smith LC . Sea urchin coelomocytes specifically express a homologue of the complement component C3. J Immunol 1998; 160:2983–2997.

   CAS  PubMed  Google Scholar 

8. Zhu Y, Thangamani S, Ho B, Ding JL . The ancient origin of the complement system. EMBO J 2005; 24:382–394.

   Article  CAS  PubMed  Google Scholar 

9. Miller DJ, Hemmrich G, Ball EE, et al. The innate immune repertoire in cnidaria–ancestral complexity and stochastic gene loss. Genome Biol 2007; 8:R59.

   Article  CAS  PubMed  PubMed Central  Google Scholar 

10. Du Pasquier L, Litman GW . Origin and Evolution of the Vertebrate Immune System. Berlin: Springer Edition, 2000.

    Book  Google Scholar 

11. Walport MJ . Complement. Second of two parts. N Engl J Med 2001; 344:1140–1144.

    Article  CAS  PubMed  Google Scholar 

12. Medzhitov R, Janeway C Jr . Innate immunity. N Engl J Med 2000; 343:338–344.

    Article  CAS  PubMed  Google Scholar 

13. Medzhitov R, Janeway CA Jr . Decoding the patterns of self and nonself by the innate immune system. Science 2002; 296:298–300.

    Article  CAS  PubMed  Google Scholar 

14. Gordon S . Pattern recognition receptors: doubling up for the innate immune response. Cell 2002; 111:927–930.

    Article  CAS  PubMed  Google Scholar 

15. Epstein J, Eichbaum Q, Sheriff S, Ezekowitz RA . The collectins in innate immunity. Curr Opin Immunol 1996; 8:29–35.

    Article  CAS  PubMed  Google Scholar 

16. Fujita T, Endo Y, Nonaka M . Primitive complement system–recognition and activation. Mol Immunol 2004; 41:103–111.

    Article  CAS  PubMed  Google Scholar 

17. Harmat V, Gal P, Kardos J, et al. The structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions. J Mol Biol 2004; 342:1533–1546.

    Article  CAS  PubMed  Google Scholar 

18. Bally I, Rossi V, Lunardi T, et al. Identification of the C1q-binding sites of human C1r and C1s: a refined three-dimensional model of the C1 complex of complement. J Biol Chem 2009; 284:19340–19348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

19. Gal P, Barna L, Kocsis A, Zavodszky P . Serine proteases of the classical and lectin pathways: similarities and differences. Immunobiology 2007; 212:267–277.

    Article  CAS  PubMed  Google Scholar 

20. Matsushita M, Endo Y, Fujita T . MASP1 (MBL-associated serine protease 1). Immunobiology 1998; 199:340–347.

    Article  CAS  PubMed  Google Scholar 

21. Dahl MR, Thiel S, Matsushita M, et al. MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Immunity 2001; 15:127–135.

    Article  CAS  PubMed  Google Scholar 

22. Takahashi M, Iwaki D, Kanno K, et al. Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway. J Immunol 2008; 180:6132–6138.

    Article  CAS  PubMed  Google Scholar 

23. Dobo J, Harmat V, Beinrohr L, et al. MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity. J Immunol 2009; 183:1207–1214.

    Article  CAS  PubMed  Google Scholar 

24. Hourcade DE . Properdin and complement activation: a fresh perspective. Curr Drug Targets 2008; 9:158–164.

    Article  CAS  PubMed  Google Scholar 

25. Paques EP, Scholze H, Huber R . Purification and crystallization of human anaphylatoxin, C3a. Hoppe Seylers Z Physiol Chem 1980; 361:977–980.

    Article  CAS  PubMed  Google Scholar 

26. Nagar B, Jones RG, Diefenbach RJ, Isenman DE, Rini JM . X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2. Science 1998; 280:1277–1281.

    Article  CAS  PubMed  Google Scholar 

27. Janssen BJ, Huizinga EG, Raaijmakers HC, et al. Structures of complement component C3 provide insights into the function and evolution of immunity. Nature 2005; 437:505–511.

    Article  CAS  PubMed  Google Scholar 

28. Milder FJ, Gomes L, Schouten A, et al. Factor B structure provides insights into activation of the central protease of the complement system. Nat Struct Mol Biol 2007; 14:224–228.

    Article  CAS  PubMed  Google Scholar 

29. Torreira E, Tortajada A, Montes T, Rodriguez de Cordoba S, Llorca O . 3D structure of the C3bB complex provides insights into the activation and regulation of the complement alternative pathway convertase. Proc Natl Acad Sci USA 2009; 106:882–887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

30. Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV . The crystal structure of C2a, the catalytic fragment of classical pathway C3 and C5 convertase of human complement. J Mol Biol 2007; 367:224–233.

    Article  CAS  PubMed  Google Scholar 

31. Hourcade DE . The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem 2006; 281:2128–2132.

    Article  CAS  PubMed  Google Scholar 

32. Spitzer D, Mitchell LM, Atkinson JP, Hourcade DE . Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J Immunol 2007; 179:2600–2608.

    Article  CAS  PubMed  Google Scholar 

33. 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; 111:732–740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

34. Huber-Lang M, Sarma JV, Zetoune FS, et al. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 2006; 12:682–687.

    Article  CAS  PubMed  Google Scholar 

35. Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD . Complement and coagulation: strangers or partners in crime? Trends Immunol 2007; 28:184–192.

    Article  CAS  PubMed  Google Scholar 

36. Liszewski MK, Farries TC, Lublin DM, Rooney IA, Atkinson JP . Control of the complement system. Adv Immunol 1996; 61:201–283.

    Article  CAS  PubMed  Google Scholar 

37. Sim RB, Day AJ, Moffatt BE, Fontaine M . Complement factor I and cofactors in control of complement system convertase enzymes. Methods Enzymol 1993; 223:13–35.

    Article  CAS  PubMed  Google Scholar 

38. Turnberg D, Botto M . The regulation of the complement system: insights from genetically-engineered mice. Mol Immunol 2003; 40:145–153.

    Article  CAS  PubMed  Google Scholar 

39. Sharma AK, Pangburn MK . Identification of three physically and functionally distinct binding sites for C3b in human complement factor H by deletion mutagenesis. Proc Natl Acad Sci USA 1996; 93:10996–11001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

40. Seya T, Hirano A, Matsumoto M, Nomura M, Ueda S . Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions. Int J Biochem Cell Biol 1999; 31:1255–1260.

    Article  CAS  PubMed  Google Scholar 

41. Wu J, Wu YQ, Ricklin D, et al. Structure of complement fragment C3b-factor H and implications for host protection by complement regulators. Nat Immunol 2009; 10:728–733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

42. Rooijakkers SH, Wu J, Ruyken M, et al. Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nat Immunol 2009; 10:721–727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

43. Blackmore TK, Hellwage J, Sadlon TA, et al. Identification of the second heparin-binding domain in human complement factor H. J Immunol 1998; 160:3342–3348.

    CAS  PubMed  Google Scholar 

44. Meri S, Morgan BP, Davies A, et al. Human protectin (CD59), an 18,000–20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology 1990; 71:1–9.

    CAS  PubMed  PubMed Central  Google Scholar 

45. Esser AF . The membrane attack complex of complement. Assembly, structure and cytotoxic activity. Toxicology 1994; 87:229–247.

    Article  CAS  PubMed  Google Scholar 

46. Papadimitriou JC, Ramm LE, Drachenberg CB, Trump BF, Shin ML . Quantitative analysis of adenine nucleotides during the prelytic phase of cell death mediated by C5b-9. J Immunol 1991; 147:212–217.

    CAS  PubMed  Google Scholar 

47. Cragg MS, Howatt WJ, Bloodworth L, et al. Complement mediated cell death is associated with DNA fragmentation. Cell Death Differ 2000; 7:48–58.

    Article  CAS  PubMed  Google Scholar 

48. Frank MM . Annihilating host defense. Nat Med 2001; 7:1285–1286.

    Article  CAS  PubMed  Google Scholar 

49. Hugli TE, Muller-Eberhard HJ . Anaphylatoxins: C3a and C5a. Adv Immunol 1978; 26:1–53.

    Article  CAS  PubMed  Google Scholar 

50. Sunyer JO, Boshra H, Li J . Evolution of anaphylatoxins, their diversity and novel roles in innate immunity: insights from the study of fish complement. Vet Immunol Immunopathol 2005; 108:77–89.

    Article  CAS  PubMed  Google Scholar 

51. Ember JA, Hugli TE . Complement factors and their receptors. Immunopharmacology 1997; 38:3–15.

    Article  CAS  PubMed  Google Scholar 

52. Lienenklaus S, Ames RS, Tornetta MA, et al. Human anaphylatoxin C4a is a potent agonist of the guinea pig but not the human C3a receptor. J Immunol 1998; 161:2089–2093.

    CAS  PubMed  Google Scholar 

53. Haas PJ, van Strijp J . Anaphylatoxins: their role in bacterial infection and inflammation. Immunol Res 2007; 37:161–175.

    Article  CAS  PubMed  Google Scholar 

54. Wetsel RA . Structure, function and cellular expression of complement anaphylatoxin receptors. Curr Opin Immunol 1995; 7:48–53.

    Article  CAS  PubMed  Google Scholar 

55. Hsu MH, Ember JA, Wang M, et al. Cloning and functional characterization of the mouse C3a anaphylatoxin receptor gene. Immunogenetics 1997; 47:64–72.

    Article  CAS  PubMed  Google Scholar 

56. Hollma TJ, Haviland DL, Kildsgaard J, Watts K, Wetsela RA . Cloning, expression, sequence determination, and chromosome localization of the mouse complement C3a anaphylatoxin receptor gene. Mol Immunol 1998; 35:137–148.

    Article  Google Scholar 

57. Bao L, Gerard NP, Eddy RL Jr, Shows TB, Gerard C . Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. Genomics 1992; 13:437–440.

    Article  CAS  PubMed  Google Scholar 

58. Haviland DL, McCoy RL, Whitehead WT, et al. Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung. J Immunol 1995; 154:1861–1869.

    CAS  PubMed  Google Scholar 

59. Monk PN, Scola AM, Madala P, Fairlie DP . Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol 2007; 152:429–448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

60. Rabiet M, Huet E, Boulay F . The N-formyl peptide receptors and the anaphylatoxin C5a receptors: an overview. Biochimie 2007; 89:1089–1106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

61. Norgauer J, Dobos G, Kownatzki E, et al. Complement fragment C3a stimulates Ca2+ influx in neutrophils via a pertussis-toxin-sensitive G protein. Eur J Biochem 1993; 217:289–294.

    Article  CAS  PubMed  Google Scholar 

62. Zwirner J, Gotze O, Moser A, et al. Blood- and skin-derived monocytes/macrophages respond to C3a but not to C3a(desArg) with a transient release of calcium via a pertussis toxin-sensitive signal transduction pathway. Eur J Immunol 1997; 27:2317–2322.

    Article  CAS  PubMed  Google Scholar 

63. Vanek M, Hawkins LD, Gusovsky F . Coupling of the C5a receptor to Gi in U-937 cells and in cells transfected with C5a receptor cDNA. Mol Pharmacol 1994; 46:832–839.

    CAS  PubMed  Google Scholar 

64. Amatruda TT III, Gerard NP, Gerard C, Simon MI . Specific interactions of chemoattractant factor receptors with G-proteins. J Biol Chem 1993; 268:10139–10144.

    CAS  PubMed  Google Scholar 

65. Buhl AM, Avdi N, Worthen GS, Johnson GL . Mapping of the C5a receptor signal transduction network in human neutrophils. Proc Natl Acad Sci USA 1994; 91:9190–9194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

66. Gasque P, Singhrao SK, Neal JW, et al. The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system: analysis in multiple sclerosis and bacterial meningitis. J Immunol 1998; 160:3543–3554.

    CAS  PubMed  Google Scholar 

67. Ischenko A, Sayah S, Patte C, et al. Expression of a functional anaphylatoxin C3a receptor by astrocytes. J Neurochem 1998; 71:2487–2496.

    Article  CAS  PubMed  Google Scholar 

68. Oksjoki R, Laine P, Helske S, et al. Receptors for the anaphylatoxins C3a and C5a are expressed in human atherosclerotic coronary plaques. Atherosclerosis 2007; 195:90–99.

    Article  CAS  PubMed  Google Scholar 

69. Mizuno M, Blanchin S, Gasque P, Nishikawa K, Matsuo S . High levels of complement C3a receptor in the glomeruli in lupus nephritis. Am J Kidney Dis 2007; 49:598–606.

    Article  CAS  PubMed  Google Scholar 

70. Lee H, Whitfeld PL, Mackay CR . Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2. Immunol Cell Biol 2008; 86:153–160.

    Article  CAS  PubMed  Google Scholar 

71. Gutzmer R, Kother B, Zwirner J, et al. Human plasmacytoid dendritic cells express receptors for anaphylatoxins C3a and C5a and are chemoattracted to C3a and C5a. J Invest Dermatol 2006; 126:2422–2429.

    Article  CAS  PubMed  Google Scholar 

72. Soruri A, Kim S, Kiafard Z, Zwirner J . Characterization of C5aR expression on murine myeloid and lymphoid cells by the use of a novel monoclonal antibody. Immunol Lett 2003; 88:47–52.

    Article  CAS  PubMed  Google Scholar 

73. Zwirner J, Fayyazi A, Gotze O . Expression of the anaphylatoxin C5a receptor in non-myeloid cells. Mol Immunol 1999; 36:877–884.

    Article  CAS  PubMed  Google Scholar 

74. Ross GD, Medof ME . Membrane complement receptors specific for bound fragments of C3. Adv Immunol 1985; 37:217–267.

    Article  CAS  PubMed  Google Scholar 

75. van Lookeren Campagne M, Wiesmann C, Brown EJ . Macrophage complement receptors and pathogen clearance. Cell Microbiol 2007; 9:2095–2102.

    Article  CAS  PubMed  Google Scholar 

76. Fearon DT . Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med 1980; 152:20–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

77. Klickstein LB, Barbashov SF, Liu T, Jack RM, Nicholson-Weller A . Complement receptor type 1 (CR1, CD35) is a receptor for C1q. Immunity 1997; 7:345–355.

    Article  CAS  PubMed  Google Scholar 

78. Ghiran I, Barbashov SF, Klickstein LB, et al. Complement receptor 1/CD35 is a receptor for mannan-binding lectin. J Exp Med 2000; 192:1797–1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

79. Krych-Goldberg M, Atkinson JP . Structure-function relationships of complement receptor type 1. Immunol Rev 2001; 180:112–122.

    Article  CAS  PubMed  Google Scholar 

80. Bacle F, Haeffner-Cavaillon N, Laude M, Couturier C, Kazatchkine MD . Induction of IL-1 release through stimulation of the C3b/C4b complement receptor type one (CR1, CD35) on human monocytes. J Immunol 1990; 144:147–152.

    CAS  PubMed  Google Scholar 

81. Molina H, Kinoshita T, Webster CB, Holers VM . Analysis of C3b/C3d binding sites and factor I cofactor regions within mouse complement receptors 1 and 2. J Immunol 1994; 153:789–795.

    CAS  PubMed  Google Scholar 

82. Ross GD . Regulation of the adhesion versus cytotoxic functions of the Mac-1/CR3/alphaMbeta2-integrin glycoprotein. Crit Rev Immunol 2000; 20:197–222.

    Article  CAS  PubMed  Google Scholar 

83. Helmy KY, Katschke KJ Jr, Gorgani NN, et al. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell 2006; 124:915–927.

    Article  CAS  PubMed  Google Scholar 

84. Nussenzweig V, Bianco C, Dukor P, Eden A . Progress in Immunology. New York: Academic, 1971.

85. Pepys MB . Role of complement in induction of the allergic response. Nat New Biol 1972; 237:157–159.

    Article  CAS  PubMed  Google Scholar 

86. Ochs HD, Wedgwood RJ, Heller SR, Beatty PG . Complement, membrane glycoproteins, and complement receptors: their role in regulation of the immune response. Clin Immunol Immunopathol 1986; 40:94–104.

    Article  CAS  PubMed  Google Scholar 

87. O'Neil KM, Ochs HD, Heller SR, et al. Role of C3 in humoral immunity. Defective antibody production in C3-deficient dogs. J Immunol 1988; 140:1939–1945.

    CAS  PubMed  Google Scholar 

88. Papamichail M, Gutierrez C, Embling P, et al. Complement dependence of localisation of aggregated IgG in germinal centres. Scand J Immunol 1975; 4:343–347.

    Article  CAS  PubMed  Google Scholar 

89. Carroll MC . The complement system in B cell regulation. Mol Immunol 2004; 41:141–146.

    Article  CAS  PubMed  Google Scholar 

90. Carroll MC . Complement and humoral immunity. Vaccine 2008; 26 Suppl 8:I28–33.

    Article  CAS  Google Scholar 

91. Kinoshita T, Thyphronitis G, Tsokos GC, et al. Characterization of murine complement receptor type 2 and its immunological cross-reactivity with type 1 receptor. Int Immunol 1990; 2:651–659.

    Article  CAS  PubMed  Google Scholar 

92. Fang Y, Xu C, Fu YX, Holers VM, Molina H . Expression of complement receptors 1 and 2 on follicular dendritic cells is necessary for the generation of a strong antigen-specific IgG response. J Immunol 1998; 160:5273–5279.

    CAS  PubMed  Google Scholar 

93. Carter RH and Fearon DT . CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 1992; 256:105–107.

    Article  CAS  PubMed  Google Scholar 

94. Dempsey PW, Allison ME, Akkaraju S, Goodnow CC, Fearon DT . C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 1996; 271:348–350.

    Article  CAS  PubMed  Google Scholar 

95. Carsetti R, Kohler G, Lamers MC . Transitional B cells are the target of negative selection in the B cell compartment. J Exp Med 1995; 181:2129–2140.

    Article  CAS  PubMed  Google Scholar 

96. Fleming SD, Shea-Donohue T, Guthridge JM, et al. Mice deficient in complement receptors 1 and 2 lack a tissue injury-inducing subset of the natural antibody repertoire. J Immunol 2002; 169:2126–2133.

    Article  CAS  PubMed  Google Scholar 

97. Reid RR, Woodcock S, Shimabukuro-Vornhagen A, et al. Functional activity of natural antibody is altered in Cr2-deficient mice. J Immunol 2002; 169:5433–5440.

    Article  CAS  PubMed  Google Scholar 

98. Ahearn JM, Fischer MB, Croix D, et al. Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity 1996; 4:251–262.

    Article  CAS  PubMed  Google Scholar 

99. Barrington RA, Zhang M, Zhong X, et al. CD21/CD19 coreceptor signaling promotes B cell survival during primary immune responses. J Immunol 2005; 175:2859–2867.

    Article  CAS  PubMed  Google Scholar 

100. Fischer MB, Goerg S, Shen L, et al. Dependence of germinal center B cells on expression of CD21/CD35 for survival. Science 1998; 280:582–585.

     Article  CAS  PubMed  Google Scholar 

101. Cyster JG, Ansel KM, Reif K, et al. Follicular stromal cells and lymphocyte homing to follicles. Immunol Rev 2000; 176:181–193.

     Article  CAS  PubMed  Google Scholar 

102. Barrington RA, Pozdnyakova O, Zafari MR, Benjamin CD, Carroll MC . B lymphocyte memory: role of stromal cell complement and FcgammaRIIB receptors. J Exp Med 2002; 196:1189–1199.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

103. Fischer W, Hugli T . Regulation of B cell functions by C3a and C3a(desArg): suppression of TNF-α, IL-6, and the polyclonal immune response. J Immunol 1997; 159:4279–4286.

     CAS  PubMed  Google Scholar 

104. Morgan EL, Weigle WO, Hugli TE . Anaphylatoxin-mediated regulation of the immune response. I. C3a-mediated suppression of human and murine humoral immune responses. J Exp Med 1982; 155:1412–1426.

     Article  CAS  PubMed  Google Scholar 

105. Morgan EL, Thoman ML, Weigle WO, Hugli TE . Anaphylatoxin-mediated regulation of the immune response. II. C5a-mediated enhancement of human humoral and T cell-mediated immune responses. J Immunol 1983; 130:1257–1261.

     CAS  PubMed  Google Scholar 

106. Kupp LI, Kosco MH, Schenkein HA, Tew JG . Chemotaxis of germinal center B cells in response to C5a. Eur J Immunol 1991; 21:2697–2701.

     Article  CAS  PubMed  Google Scholar 

107. Ottonello L, Corcione A, Tortolina G, et al. rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues. J Immunol 1999; 162:6510–6517.

     CAS  PubMed  Google Scholar 

108. Fearon DT, Carroll MC . Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu Rev Immunol 2000; 18:393–422.

     Article  CAS  PubMed  Google Scholar 

109. Guinamard R, Okigaki M, Schlessinger J, Ravetch JV . Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response. Nat Immunol 2000; 1:31–36.

     Article  CAS  PubMed  Google Scholar 

110. Pozdnyakova O, Guttormsen HK, Lalani FN, Carroll MC, Kasper DL . Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3- and complement receptor 2-deficient mice. J Immunol 2003; 170:84–90.

     Article  CAS  PubMed  Google Scholar 

111. Molina H, Holers VM, Li B, et al. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc Natl Acad Sci USA 1996; 93:3357–3361.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

112. Da Costa XJ, Brockman MA, Alicot E, et al. Humoral response to herpes simplex virus is complement-dependent. Proc Natl Acad Sci USA 1999; 96:12708–12712.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

113. Mehlhop E, Diamond MS . Protective immune responses against West Nile virus are primed by distinct complement activation pathways. J Exp Med 2006; 203:1371–1381.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

114. Haas KM, Hasegawa M, Steeber DA, et al. Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responses. Immunity 2002; 17:713–723.

     Article  CAS  PubMed  Google Scholar 

115. Janeway CA Jr . Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989; 54 Pt 1:1–13.

     Article  CAS  PubMed  Google Scholar 

116. Gustavsson S, Kinoshita T, Heyman B . Antibodies to murine complement receptor 1 and 2 can inhibit the antibody response in vivo without inhibiting T helper cell induction. J Immunol 1995; 154:6524–6528.

     CAS  PubMed  Google Scholar 

117. Kopf M, Abel B, Gallimore A, Carroll M, Bachmann MF . Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat Med 2002; 8:373–378.

     Article  CAS  PubMed  Google Scholar 

118. Kim AHJ, Dimitriou ID, Holland MCH, et al. Complement C5a receptor is essential for the optimal generation of antiviral CD8+ T cell responses. J Immunol 2004; 173:2524–2529.

     Article  CAS  PubMed  Google Scholar 

119. Peng Q, Li K, Anderson K, et al. Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction. Blood 2008; 111:2452–2461.

     Article  CAS  PubMed  Google Scholar 

120. Fang C, Miwa T, Shen H, Song W . Complement-dependent enhancement of CD8+ T cell immunity to lymphocytic choriomeningitis virus infection in decay-accelerating factor-deficient mice. J Immunol 2007; 179:3178–3186.

     Article  CAS  PubMed  Google Scholar 

121. Li K, Anderson KJ, Peng Q, et al. Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation. Blood 2008; 112:5084–5094.

     Article  CAS  PubMed  Google Scholar 

122. Liu J, Miwa T, Hilliard B, et al. The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. J Exp Med 2005; 201:567–577.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

123. Heeger PS, Lalli PN, Lin F, et al. Decay-accelerating factor modulates induction of T cell immunity. J Exp Med 2005; 201:1523–1530.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

124. Liu J, Lin F, Strainic MG, et al. IFN-γ and IL-17 production in experimental autoimmune encephalomyelitis depends on local APC-T cell complement production. J Immunol 2008; 180:5882–5889.

     Article  CAS  PubMed  Google Scholar 

125. Strainic MG, Liu J, Huang D, et al. Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity 2008; 28:425–435.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

126. Lalli PN, Strainic MG, Yang M, Lin F, Medof ME, Heeger PS . Locally produced C5a binds to T cell-expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis. Blood 2008; 112:1759–1766.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

127. Zhou W, Patel H, Li K, Peng Q, Villiers MB, Sacks SH . Macrophages from C3-deficient mice have impaired potency to stimulate alloreactive T cells. Blood 2006; 107:2461–2469.

     Article  CAS  PubMed  Google Scholar 

128. Martin U, Bock D, Arseniev L, et al. The human C3a receptor is expressed on neutrophils and monocytes, but not on B or T lymphocytes. J Exp Med 1997; 186:199–207.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

129. Werfel T, Kirchhoff K, Wittmann M, et al. Activated human T lymphocytes express a functional C3a receptor. J Immunol 2000; 165:6599–6605.

     Article  CAS  PubMed  Google Scholar 

130. Zwirner J, Götze O, Begemann G, Kapp A, Kirchhoff K, Werfel T . Evaluation of C3a receptor expression on human leucocytes by the use of novel monoclonal antibodies. Immunology 1999; 97:166–172.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

131. Nataf S, Davoust N, Ames RS, Barnum SR . Human T cells express the C5a receptor and are chemoattracted to C5a. J Immunol 1999; 162:4018–4023.

     CAS  PubMed  Google Scholar 

132. Hopken UE, Lu B, Gerard NP, Gerard C . The C5a chemoattractant receptor mediates mucosal defence to infection. Nature 1996; 383:86–89.

     Article  CAS  PubMed  Google Scholar 

133. Zhang X, Kimura Y, Fang C, et al. Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo. Blood 2007; 110:228–236.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

134. Hawlisch H, Kohl J . Complement and Toll-like receptors: key regulators of adaptive immune responses. Mol Immunol 2006; 43:13–21.

     Article  CAS  PubMed  Google Scholar 

135. Iwasaki A, Medzhitov R . Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004; 5:987–995.

     Article  CAS  PubMed  Google Scholar 

136. Cattaneo R . Four viruses, two bacteria, and one receptor: membrane cofactor protein (CD46) as pathogens' magnet. J Virol 2004; 78:4385–4388.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

137. Karp CL, Wysocka M, Wahl LM, et al. Mechanism of suppression of cell-mediated immunity by measles virus. Science 1996; 273:228–231.

     Article  CAS  PubMed  Google Scholar 

138. Wagner C, Ochmann C, Schoels M, et al. The complement receptor 1, CR1 (CD35), mediates inhibitory signals in human T-lymphocytes. Mol Immunol 2006; 43:643–651.

     Article  CAS  PubMed  Google Scholar 

139. Capasso M, Durrant LG, Stacey M, Gordon S, Ramage J, Spendlove I . Costimulation via CD55 on human CD4+ T cells mediated by CD97. J Immunol 2006; 177:1070–1077.

     Article  CAS  PubMed  Google Scholar 

140. Mold C . Role of complement in host defense against bacterial infection. Microbes Infect 1999; 1:633–638.

     Article  CAS  PubMed  Google Scholar 

141. Ross SC, Densen P . Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 1984; 63:243–273.

     Article  CAS  PubMed  Google Scholar 

142. Orren A, Potter PC, Cooper RC, du Toit E . Deficiency of the sixth component of complement and susceptibility to Neisseria meningitidis infections: studies in 10 families and five isolated cases. Immunology 1987; 62:249–253.

     CAS  PubMed  PubMed Central  Google Scholar 

143. Summerfield JA, Sumiya M, Levin M, Turner MW . Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. BMJ 1997; 314:1229–1232.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

144. Rooijakkers SH, van Strijp JA . Bacterial complement evasion. Mol Immunol 2007; 44:23–32.

     Article  CAS  PubMed  Google Scholar 

145. Silverman GJ, Goodyear CS, Siegel DL . On the mechanism of staphylococcal protein A immunomodulation. Transfusion 2005; 45:274–280.

     Article  CAS  PubMed  Google Scholar 

146. Rooijakkers SH, Ruyken M, Roos A, et al. Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases. Nat Immunol 2005; 6:920–927.

     Article  CAS  PubMed  Google Scholar 

147. Schmidtchen A, Holst E, Tapper H, Bjorck L . Elastase-producing Pseudomonas aeruginosa degrade plasma proteins and extracellular products of human skin and fibroblasts, and inhibit fibroblast growth. Microb Pathog 2003; 34:47–55.

     Article  CAS  PubMed  Google Scholar 

148. Joiner KA, Warren KA, Brown EJ, Swanson J, Frank MM . Studies on the mechanism of bacterial resistance to complement-mediated killing. IV. C5b-9 forms high molecular weight complexes with bacterial outer membrane constituents on serum-resistant but not on serum-sensitive Neisseria gonorrhoeae. J Immunol 1983; 131:1443–1451.

     CAS  PubMed  Google Scholar 

149. Joiner K, Brown E, Hammer C, Warren K, Frank M . Studies on the mechanism of bacterial resistance to complement-mediated killing. III. C5b-9 deposits stably on rough and type 7 S. pneumoniae without causing bacterial killing. J Immunol 1983; 130:845–849.

     CAS  PubMed  Google Scholar 

150. Pausa M, Pellis V, Cinco M, et al. Serum-resistant strains of Borrelia burgdorferi evade complement-mediated killing by expressing a CD59-like complement inhibitory molecule. J Immunol 2003; 170:3214–3222.

     Article  CAS  PubMed  Google Scholar 

151. Horstmann RD, Sievertsen HJ, Knobloch J, Fischetti VA . Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci USA 1988; 85:1657–1661.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

152. Ngampasutadol J, Ram S, Gulati S, et al. Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion. J Immunol 2008; 180:3426–3435.

     Article  CAS  PubMed  Google Scholar 

153. Schneider MC, Prosser BE, Caesar JJ, et al. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature 2009; 458:890–893.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

154. Lubinski J, Nagashunmugam T, Friedman HM . Viral interference with antibody and complement. Semin Cell Dev Biol 1998; 9:329–337.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

155. de Haas CJ, Veldkamp KE, Peschel A, et al. Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med 2004; 199:687–695.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

156. Postma B, Poppelier MJ, van Galen JC, et al. Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol 2004; 172:6994–7001.

     Article  CAS  PubMed  Google Scholar 

157. Dorig RE, Marcil A, Chopra A, Richardson CD . The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 1993; 75:295–305.

     Article  CAS  PubMed  Google Scholar 

158. Lindahl G, Sjobring U, Johnsson E . Human complement regulators: a major target for pathogenic microorganisms. Curr Opin Immunol 2000; 12:44–51.

     Article  CAS  PubMed  Google Scholar 

159. Kallstrom H, Liszewski MK, Atkinson JP, Jonsson AB . Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol Microbiol 1997; 25:639–647.

     Article  CAS  PubMed  Google Scholar 

160. Evans DJ, Almond JW . Cell receptors for picornaviruses as determinants of cell tropism and pathogenesis. Trends Microbiol 1998; 6:198–202.

     Article  CAS  PubMed  Google Scholar 

161. Shafren DR, Dorahy DJ, Ingham RA, Burns GF, Barry RD . Coxsackievirus A21 binds to decay-accelerating factor but requires intercellular adhesion molecule 1 for cell entry. J Virol 1997; 71:4736–4743.

     CAS  PubMed  PubMed Central  Google Scholar 

162. Tanner J, Weis J, Fearon D, Whang Y, and Kieff E . Epstein-Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell 1987; 50:203–213.

     Article  CAS  PubMed  Google Scholar 

163. Stoiber H, Clivio A, Dierich MP . Role of complement in HIV infection. Annu Rev Immunol 1997; 15:649–674.

     Article  CAS  PubMed  Google Scholar 

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The complement pathway. Complement can be activated through three pathways: classical, lectin, and alternative. The classical pathway is activated when C1q binds to antibody attached to antigen, activating C1r and C1s, which cleave C4 and C2. The lectin pathway is activated when mannose-binding lectin (MBL) encounters conserved pathogenic carbohydrate motifs, activating the MBL-associated serine proteases (MASPs) and again cleaving C4 and C2. C4 and C2 cleavage products form the classical and lectin pathway C3 convertase, C4bC2a, which cleaves C3 into C3b and C3a. A second molecule of C3b can associate with C4bC2a to form the C5 convertase of the classical and lectin pathways, C4bC2aC3b. The alternative pathway (AP) is activated when C3 undergoes spontaneous hydrolysis and forms the initial AP C3 convertase, C3(H2O)Bb, in the presence of Factors B and D, leading to additional C3 cleavage and eventual formation of the AP C3 convertase (C3bBb) and AP C5 convertase (C3bBbC3b). Properdin facilitates AP activation by stabilizing AP convertases. All three pathways culminate in the formation of the convertases, which in turn generate the major effectors of the complement system: anaphylatoxins (C4a/C3a/C5a), the membrane attack complex (MAC), and opsonins (e.g., C3b). Anaphylatoxins are potent proinflammatory molecules derived from the cleavage of C4, C3, and C5. The MAC is a terminal assembly of complement components C5b through C9, which can directly lyse targeted surfaces. C3b induces phagocytosis of opsonized targets and also serves to amplify complement activation through the AP.