C4a: An Anaphylatoxin in Name only

Journal of Innate Immunity

Volumn 7, Issue 4, 2015, Pages 333-339

  Barnum, Scott R ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

Anaphylatoxin; Complement; G protein coupled receptors

Indexed keywords

ANAPHYLATOXIN; ANAPHYLATOXIN RECEPTOR; COMPLEMENT COMPONENT C4A; LEUKOTRIENE RECEPTOR; UNCLASSIFIED DRUG; C3 PROTEIN, HUMAN; COMPLEMENT COMPONENT C3; COMPLEMENT COMPONENT C5A;

CHEMICAL STRUCTURE; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; COMPLEMENT ACTIVATION; INFLAMMATION; NOMENCLATURE;

COMPLEMENT ACTIVATION; COMPLEMENT C3; COMPLEMENT C4A; COMPLEMENT C5A; HUMANS; INFLAMMATION; TERMINOLOGY AS TOPIC;

EID: 84937524490     PISSN: 1662811X     EISSN: 16628128     Source Type: Journal    
DOI: 10.1159/000371423     Document Type: Review

References (80)

1. Rutkowski MJ, Sughrue ME, Kane AJ, Ahn BJ, Fang S, Parsa AT: The complement cascade as a mediator of tissue growth and regeneration. Inflamm Res 2010; 59: 897-905.
2. Rutkowski MJ, Sughrue ME, Kane AJ, Mills SA, Fang S, Parsa AT: Complement and the central nervous system: emerging roles in development, protection and regeneration. Immunol Cell Biol 2010; 88: 781-786.
3. Klos A, Tenner AJ, Johswich KO, Ager RR, Reis ES, Kohl J: The role of the anaphylatoxins in health and disease. Mol Immunol 2009; 46: 2753-2766.
4. Klos A, Wende E, Wareham KJ, Monk PN: International union of basic and clinical pharmacology. LXXXVII. Complement peptide c5a, c4a, and c3a receptors. Pharmacol Rev 2013; 65: 500-543.
5. Kimura Y, Madhavan M, Call MK, Santiago W, Tsonis PA, Lambris JD, Del Rio-Tsonis K: Expression of complement 3 and complement 5 in newt limb and lens regeneration. J Immunol 2003; 170: 2331-2339.
6. Stephan AH, Barres BA, Stevens B: The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci 2012; 35: 369-389.
7. Schupf N, Williams CA, Hugli TE, Cox J: Psychopharmacological activity of anaphylatoxin C3a in rat hypothalamus. J Neuroimmunol 1983; 5: 305-316.
8. Williams CA, Schupf N, Hugli TE: Anaphylatoxin C5a modulation of an alpha-adrenergic receptor system in the rat hypothalamus. J Neuroimmunol 1985; 9: 29-40.
9. Schupf N, Williams CA, Berkman A, Cattell WS, Kerper L: Binding specificity and presynaptic action of anaphylatoxin C5a in rat brain. Brain Behav Immun 1989; 3: 28-38.
10. Ohinata K, Inui A, Asakawa A, Wada K, Wada E, Yoshikawa M: Albutensin A and complement C3a decrease food intake in mice. Peptides 2002; 23: 127-133.
11. Ohinata K, Takagi K, Biyajima K, Kaneko K, Miyamoto C, Asakawa A, Eguchi N, Urade Y, Inui A, Yoshikawa M: Complement C5a stimulates food intake via a prostaglandin D(2)-and neuropeptide Y-dependent mechanism in mice. Prostaglandins Other Lipid Mediat 2009; 90: 81-84.
12. Ohinata K, Yoshikawa M: Food intake regulation by central complement system. Adv Exp Med Biol 2008; 632: 35-46.
13. Ember JA, Jagels MA, Hugli TE: Characterization of complement anaphylatoxina and their biological responses; in Volanakis JE, Frank MM (eds): The Human Complement System in Health and Disease. New York, Dekker, 1998, pp 241-284.
14. Fernandez HN, Hugli TE: Primary structural analysis of the polypeptide portion of human c5a anaphylatoxin: polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. J Biol Chem 1978; 253: 6955-6964.
15. Nettesheim DG, Edalji RP, Mollison KW, Greer J, Zuiderweg ER: Secondary structure of complement component C3a anaphylatoxin in solution as determined by NMR spectroscopy: differences between crystal and solution conformations. Proc Natl Acad Sci USA 1988; 85: 5036-5040.
16. Zhang X, Boyar W, Toth MJ, Wennogle L, Gonnella NC: Structural definition of the C5a C terminus by two-dimensional nuclear magnetic resonance spectroscopy. Proteins 1997; 28: 261-267.
17. Zuiderweg ER, Nettesheim DG, Mollison KW, Carter GW: Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data. Biochemistry 1989; 28: 172-185.
18. Hugli TE: Human anaphylatoxin (C3a) from the third component of complement: primary structure. J Biol Chem 1975; 250: 8293-8301.
19. Moon KE, Gorski JP, Hugli TE: Complete primary structure of human C4a anaphylatoxin. J Biol Chem 1981; 256: 8685-8692.
20. Hugli TE, Vallota EH, Muller-Eberhard HJ: Purification and partial characterization of human and porcine C3a anaphylatoxin. J Biol Chem 1975; 250: 1472-1478.
21. Smith MA, Gerrie LM, Dunbar B, Fothergill JE: Primary structure of bovine complement activation fragment C4a, the third anaphylatoxin: purification and complete amino acid sequence. Biochem 1982; 207: 253-260.
22. Cui L, Carney DF, Hugli TE: Primary structure and functional characterization of rat C5a: an anaphylatoxin with unusually high potency. Protein Sci 1994; 3: 1169-1177.
23. Wetsel RA, Lemons RS, Le Beau MM, Barnum SR, Noack D, Tack BF: Molecular analysis of human complement component C5: localization of the structural gene to chromosome 9. Biochemistry 1988; 27: 1474-1482.
24. Huber R, Scholze H, Paques EP, Deisenhofer J: Crystal structure analysis and molecular model of human C3a anaphylatoxin. Hoppe Seylers Z Physiol Chem 1980; 361: 1389-1399.
25. Paques EP, Scholze H, Huber R: Purification and crystallization of human anaphylatoxin, C3a. Hoppe Seylers Z Physiol Chem 1980; 361: 977-980.
26. Greer J: Comparative structural anatomy of the complement anaphylatoxin proteins C3a, C4a and C5a. Enzyme 1986; 36: 150-163.
27. Pasupuleti M, Walse B, Nordahl EA, Morgelin M, Malmsten M, Schmidtchen A: Preservation of antimicrobial properties of complement peptide C3a, from invertebrates to humans. J Biol Chem 2007; 282: 2520-2528.
28. Fredslund F, Laursen NS, Roversi P, Jenner L, Oliveira CL, Pedersen JS, Nunn MA, Lea SM, Discipio R, Sottrup-Jensen L, Andersen GR: Structure of and influence of a tick complement inhibitor on human complement component 5. Nat Immunol 2008; 9: 753-760.
29. Ames RS, Tornetta MA, Foley JJ, Hugli TE, Sarau HM: Evidence that the receptor for C4a is distinct from the C3a receptor. Immunopharmacology 1997; 38: 87-92.
30. Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, Zeng Z, Su K, Jurewicz AJ, Hertzberg RP, Bergsma DJ, Kumar C: Molecular cloning and characterization of the human anaphylatoxin C3a receptor. J Biol Chem 1996; 271: 20231-20234.
31. Crass T, Raffetseder U, Martin U, Grove M, Klos A, Kohl J, Bautsch W: Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from differentiated U-937 cells. Eur J Immunol 1996; 26: 1944-1950.
32. Tsuruta T, Yamamoto T, Matsubara S, Nagasawa S, Tanase S, Tanaka J, Takagi K, Kambara T: Novel function of C4a anaphylatoxin: release from monocytes of protein which inhibits monocyte chemotaxis. Am J Pathol 1993; 142: 1848-1857.
33. Kato Y, Nakao M, Shimizu M, Wariishi H, Yano T: Purification and functional assessment of c3a, c4a and c5a of the common carp (Cyprinus carpio) complement. Dev Comp Immunol 2004; 28: 901-910.
34. Gorski JP, Hugli TE, Muller-Eberhard HJ: C4a: The third anaphylatoxin of the human complement system. Proc Natl Acad Sci USA 1979; 76: 5299-5302.
35. Hugli TE, Kawahara MS, Unson CG, Molinar-Rode R, Erickson BW: The active site of human C4a anaphylatoxin. Mol Immunol 1983; 20: 637-645.
36. Fukuoka Y, Xia HZ, Sanchez-Munoz LB, Dellinger AL, Escribano L, Schwartz LB: Generation of anaphylatoxins by human beta-tryptase from C3, C4, and C5. J Immunol 2008; 180: 6307-6316.
37. Meuer S, Ecker U, Hadding U, Bitter-Suermann D: Platelet-serotonin release by C3a and C5a: Two independent pathways of activation. J Immunol 1981; 126: 1506-1509.
38. Meuer S, Hugli TE, Andreatta RH, Hadding U, Bitter-Suermann D: Comparative study on biological activities of various anaphylatoxins (C4a, C3a, C5a): investigations on their ability to induce platelet secretion. Inflammation 1981; 5: 263-273.
39. Raedler H, Vieyra MB, Leisman S, Lakhani P, Kwan W, Yang M, Johnson K, Faas SJ, Tamburini P, Heeger PS: Anti-complement component C5 mAB synergizes with CTLA4Ig to inhibit alloreactive T cells and prolong cardiac allograft survival in mice. Am J Transplant 2011; 11: 1397-1406.
40. Vieyra M, Leisman S, Raedler H, Kwan WH, Yang M, Strainic MG, Medof ME, Heeger PS: Complement regulates CD4 T-cell help to CD8 T cells required for murine allograft rejection. Am J Pathol 2011; 179: 766-774.
41. 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.
42. Liu J, Lin F, Strainic MG, An F, Miller RH, Altuntas CZ, Heeger PS, Tuohy VK, Medof ME: IFN-gamma and IL-17 production in experimental autoimmune encephalomyelitis depends on local APC-T cell complement production. J Immunol 2008; 180: 5882-5889.
43. Strainic MG, Liu J, Huang D, An F, Lalli PN, Muqim N, Shapiro VS, Dubyak GR, Heeger PS, Medof ME: Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells. Immunity 2008; 28: 425-435.
44. Han G, Geng S, Li Y, Chen G, Wang R, Li X, Ma Y, Shen B, Li Y: GammadeltaT-cell function in sepsis is modulated by C5a receptor signalling. Immunology 2011; 133: 340-349.
45. Liu Z, Eltoum IE, Guo B, Beck BH, Cloud GA, Lopez RD: Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer. J Immunol 2008; 180: 6044-6053.
46. Benard M, Raoult E, Vaudry D, Leprince J, Falluel-Morel A, Gonzalez BJ, Galas L, Vaudry H, Fontaine M: Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Mol Immunol 2008; 45: 3767-3774.
47. Shinjyo N, Stahlberg A, Dragunow M, Pekny M, Pekna M: Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells. Stem Cells 2009; 27: 2824-2832.
48. Carmona-Fontaine C, Theveneau E, Tzekou A, Tada M, Woods M, Page KM, Parsons M, Lambris JD, Mayor R: Complement fragment C3a controls mutual cell attraction during collective cell migration. Dev Cell 2011; 21: 1026-1037.
49. Jalili A, Shirvaikar N, Marquez-Curtis L, Qiu Y, Korol C, Lee H, Turner AR, Ratajczak MZ, Janowska-Wieczorek A: Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. Exp Hematol 2010; 38: 321-332.
50. Strey CW, Markiewski M, Mastellos D, Tudoran R, Spruce LA, Greenbaum LE, Lambris JD: The proinflammatory mediators C3a and C5a are essential for liver regeneration. J Exp Med 2003; 198: 913-923.
51. Haynes T, Luz-Madrigal A, Reis ES, Echeverri Ruiz NP, Grajales-Esquivel E, Tzekou A, Tsonis PA, Lambris JD, Del Rio-Tsonis K: Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regeneration. Nat Commun 2013; 4: 2312.
52. Malmsten M, Davoudi M, Walse B, Rydengard V, Pasupuleti M, Morgelin M, Schmidtchen A: Antimicrobial peptides derived from growth factors. Growth Factors 2007; 25: 60-70.
53. Nordahl EA, Rydengard V, Nyberg P, Nitsche DP, Morgelin M, Malmsten M, Bjorck L, Schmidtchen A: Activation of the complement system generates antibacterial peptides. Proc Natl Acad Sci USA 2004; 101: 16879-16884.
54. Gao Z, Li M, Wu J, Zhang S: Interplay between invertebrate C3a with vertebrate macrophages: functional characterization of immune activities of amphioxus C3a. Fish Shellfish Immunol 2013; 35: 1249-1259.
55. Zhao Y, Xu H, Yu W, Xie BD: Complement anaphylatoxin C4a inhibits C5a-induced neointima formation following arterial injury. Mol Med Rep 2014; 10: 45-52.
56. Murakami Y, Yamamoto T, Imamichi T, Nagasawa S: Cellular responses of guinea-pig macrophages to C4a: inhibition of C3a-induced O 2-generation by C4a. Immunol Lett 1993; 36: 301-304.
57. Yount NY, Bayer AS, Xiong YQ, Yeaman MR: Advances in antimicrobial peptide immunobiology. Biopolymers 2006; 84: 435-458.
58. Gerard NP, Gerard C: The chemotactic receptor for human C5a anaphylatoxin. Nature 1991; 349: 614-617.
59. Roglic A, Prossnitz ER, Cavanagh SL, Pan Z, Zou A, Ye RD: cDNA cloning of a novel G protein-coupled receptor with a large extracellular loop structure. Biochim Biophys Acta 1996; 1305: 39-43.
60. Ohno M, Hirata T, Enomoto M, Araki T, Ishimaru H, Takahashi TA: A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells. Mol Immunol 2000; 37: 407-412.
61. Rosenbaum DM, Rasmussen SG, Kobilka BK: The structure and function of G-proteincoupled receptors. Nature 2009; 459: 356-363.
62. Joost P, Methner A: Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction of orphan receptor ligands. Genome Biol 2002; 3:RESEARCH0063.
63. Wilken HC, Gotze O, Werfel T, Zwirner J: C3a(desArg) does not bind to and signal through the human C3a receptor. Immunol Lett 1999; 67: 141-145.
64. Johswich K, Martin M, Thalmann J, Rheinheimer C, Monk PN, Klos A: Ligand specificity of the anaphylatoxin C5L2 receptor and its regulation on myeloid and epithelial cell lines. J Biol Chem 2006; 281: 39088-39095.
65. Crass T, Ames RS, Sarau HM, Tornetta MA, Foley JJ, Kohl J, Klos A, Bautsch W: Chimeric receptors of the human C3a receptor and C5a receptor (CD88). J Biol Chem 1999; 274: 8367-8370.
66. Chao TH, Ember JA, Wang M, Bayon Y, Hugli TE, Ye RD: Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function. J Biol Chem 1999; 274: 9721-9728.
67. Sun J, Ember JA, Chao TH, Fukuoka Y, Ye RD, Hugli TE: Identification of ligand effector binding sites in transmembrane regions of the human G protein-coupled C3a receptor. Protein Sci 1999; 8: 2304-2311.
68. Nikiforovich GV, Baranski TJ: Structural mechanisms of constitutive activation in the C5a receptors with mutations in the extracellular loops: molecular modeling study. Proteins 2012; 80: 71-80.
69. Nikiforovich GV, Marshall GR, Baranski TJ: Modeling molecular mechanisms of binding of the anaphylatoxin C5a to the C5a receptor. Biochemistry 2008; 47: 3117-3130.
70. Nikiforovich GV, Marshall GR, Baranski TJ: Simplified modeling approach suggests structural mechanisms for constitutive activation of the C5a receptor. Proteins 2011; 79: 787-802.
71. Lienenklaus S, Ames RS, Tornetta MA, Sarau HM, Foley JJ, Crass T, Sohns B, Raffetseder U, Grove M, Holzer A, Klos A, Kohl J, Bautsch W: Human anaphylatoxin C4a is a potent agonist of the guinea pig but not the human C3a receptor. J Immunol 1998; 161: 2089-2093.
72. Zinsser H: On anaphylatoxins and endotoxins of the typhoid bacillus. J Exp Med 1913; 17: 117-131.
73. Schwab L, Moll FC, Hall T, Brean H, Kirk M, van Zandt Hawn C, Janeway CA: Experimental hypersensitivity in the rabbit: effect of inhibition of antibody formation by X-radiation and nitrogen mustards on the histologic and serologic sequences, and on the behavior of serum complement, following single large injections of foreign proteins. J Exp Med 1950; 91: 505-526.
74. Osler AG, Hawrisiak MM, Ovary Z, Siqueira M, Bier OG: Studies on the mechanism of hypersensitivity phenomena. 2. The participation of complement in passive cutaneous anaphylaxis of the albino rat. J Exp Med 1957; 106: 811-834.
75. Osler AG, Randall HG, Hill BM, Ovary Z: Studies on the mechanism of hypersensitivity phenomena. 3. The participation of complement in the formation of anaphylatoxin. J Exp Med 1959; 110: 311-339.
76. Jensen J: Anaphylatoxin in its relation to the complement system. Science 1967; 155: 1122-1123.
77. da Silva WD, Eisele JW, Lepow IH: Complement as a mediator of inflammation. 3. Purification of the activity with anaphylatoxin properties generated by interaction of the first four components of complement and its identification as a cleavage product of C'3. J Exp Med 1967; 126: 1027-1048.
78. Cochrane CG, Muller-Eberhard HJ: The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med 1968; 127: 371-386.
79. Boshra H, Wang T, Hove-Madsen L, Hansen J, Li J, Matlapudi A, Secombes CJ, Tort L, Sunyer JO: Characterization of a C3a receptor in rainbow trout and Xenopus: the first identification of C3a receptors in nonmammalian species. J Immunol 2005; 175: 2427-2437.
80. 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.