Structure and Function of C3a Anaphylatoxin*

  • T. E. Hugli
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 153)

Abstract

The C3a molecule is one of three activation fragments from the complement cascade, a family of factors that include C3a, C4a, and C5a. Early recognition that more than one bio active fragment was generated during complement activation cascade must be credited to COCHRANE and MÜLLER-EBERHARD (1968) and to DIAS DA SILVA et al. (1967). These investigators were the first to use purified components of human complement to demonstrate, and then to characterize, the activation fragment from C3. In previous studies complement was activated in serum, and the bioassays that were used detected only the factor C5a (actually C5adesArg). DIAS DA SILVA et al. realized, even using purified components of the complement C1 esterase, C4, C2, and C3, that the anaphylatoxin released from C3 was not stablized unless the digest was acidified to pH 2-5, according to earlier observations of STEGEMANN et al. (1964). Later work by BOKISCH and MüLLER-EBERHARD (1970) would explain why the acid treatment was successful. Acidification presumably prevented residual carboxypeptidase (serum carboxypeptide N) in the isolates from removing an essential C-terminal arginine and inactivating the newly formed C3a anaphylatoxin. It was this lability of C3a bioactivity in serum that had prevented its discovery prior to isolation and activation of the purified components. These investigators went on to separate an active principal from the larger protein components in the reconstituted C3—C3 convertase system by gel filtration. They demonstrated that the lower molecular weight factor: (a) induced smooth-muscle contraction and was tachyphylactic to itself but not cross-tachyphylactic to the C5-derived anaphylatoxin; (b) enhanced vascular permeability when injected into skin; (c) degranulated guinea pig ileal mast cells; and (d) promoted histamine release from rat peritoneal mast cells. DIAS DA SILVA’S group originally termed the active fragment F(a)C3, i.e., activation (a) fragment from the third component of complement. COCHRANE and MüLLER-EBERHARD identified the fragment as the C3 anaphylatoxin, assuming it to be an analog to the “classical” C5a anaphylatoxin. We will refer to the fragment here primarily as C3a because the biologic action of the factor is not anaphylactoid in nature, and anaphylatoxin is functionally an inaccurate designation. However, the recognized nomenclature from common usage still refers to fragments C3a, C4a, and C5a collectively as anaphylatoxins.

Keywords

Heparin Polypeptide Arginine Alanine Disulfide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Becker S, Meuer S, Hadding U, Bitter-Suermann D (1978a) Platelet activation: a new biological activity of guinea-pig C3a anaphylatoxin. Scand J Immunol 7: 173–180PubMedGoogle Scholar
  2. Becker S, Hadding U, Schorlemmer HU, Bitter-Suermann D (1978b) Demonstration of high-affinity binding sites for C3a anaphylatoxin on guinea-pig platelets. Scand J Immunol 8; 551–555PubMedGoogle Scholar
  3. Belmont HM, Hopkins P, Edelson HS, Kaplan HB, Ludewig R, Weissmann G, Abramson S (1966) Complement activation during systemic lupus erythematous. C3a and C5a anaphylato-ins circulate during exacerbations of disease. Arthritis Rheum 29: 1085–1089Google Scholar
  4. Bitter-Suermann D, Burger R (1986) Guinea pigs deficient in C2, C4, C3 or the C3a receptor. Prog. Allergy 39: 134–158PubMedGoogle Scholar
  5. Bitter-Suermann D, Becker S, Meuer S, Schorlemmer HU, Hadding U, Andreatta R (1980) Comparative study on biological effects of the guinea pig complement-peptide C3a-related synthetic oligopeptides. Mol Immunol 17: 1257–1261PubMedGoogle Scholar
  6. Björk J, Hugh TE, Smedegård G (1985) Microvascular effects of anaphylatoxins C3a and C5a. J Immunol 134: 1115–1119PubMedGoogle Scholar
  7. Bokisch VA, Müller-Eberhard HJ (1970) Anaphylatoxin inactivator of human plasma: Its isolation and characterization as a carboxypeptidase. J Clin Invest 49: 2427–2436PubMedGoogle Scholar
  8. Burger R, Bader A, Kirschfmk M, Rother U, Schrod L, Wörner I, Zilow G (1987) Functional analysis and quantification of the complement C3 derived anaphylatoxin C3a with a monoclonal antibody. Clin Exp Immunol 68: 703–711PubMedGoogle Scholar
  9. Burger R, Zilow G, Bader A, Friedlein A, Naser W (1988) The C terminus of the anaphylatoxin C3a generated upon complement activation represents a neoantigenic determinant with diagnostic potential. J Immunol 141: 553–558PubMedGoogle Scholar
  10. Caporale LH, Tippett PS, Ericson BW, Hugli TE (1980) The active site of C3a anaphylatoxin. J Biol Chem 255: 10758–10763PubMedGoogle Scholar
  11. Charriaut C, Senik A, Kolb JP, Barel M, Frade R (1982) Inhibition of iü vitro natural killer activity by the third component of complement: role for the C3a fragment. Proc Natl Acad Sci USA 79: 6003–6007PubMedGoogle Scholar
  12. Chazin WJ, Hugli TE, Wright PE (1988) 1H NMR studies of human C3a anaphylatoxin in solution: sequential resonance assignments, secondary structure, and global fold. Biochemistry 27: 9139–9148PubMedGoogle Scholar
  13. Chenoweth DE, Hugli TE (1982) Assays for chemotactic factors and anaphylatoxins. In: Immunologic analysis. Masson, Paris, pp 227–237 (Recent progress in diagnostic laboratory immunology, chap 22)Google Scholar
  14. Chenoweth DE, Stewart RW, Cooper SW, Blackstone EH, Kirklin JW, Hugli TE (1981) Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med 304: 497–503PubMedGoogle Scholar
  15. Chenoweth DE, Cheung AK, Henderson LW (1983) Anaphylatoxin formation during hemodialy-sis: effects of different dialyzer membranes. Kidney Int 24: 764–769PubMedGoogle Scholar
  16. Chou PY, Fasman GD (1978) Empirical predictions of protein conformation. Annu Rev Biochem 47: 251–276PubMedGoogle Scholar
  17. Cochrane CG, Müller-Eberhard HJ (1968) The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med 127:371–386PubMedGoogle Scholar
  18. Corbin NC, Hugli TE (1976) The primary structure of porcine C3a anaphylatoxin. J Immunol 117: 990–995PubMedGoogle Scholar
  19. Craddock PR, Hammerschmidt D, White JG, Dalmasso AP, Jacob HS (1977) Complement (C5a)-indicated granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia. J Clin Invest 60: 260–264PubMedGoogle Scholar
  20. Cui L, Ferreri K, Hugli TE (1988) Structural characterization of the C4a anaphylatoxin from rat. Mol Immunol 25: 663–671PubMedGoogle Scholar
  21. Dawson P, Turner MW, Bradshaw A, Westaby S (1983) Complement activation and generation of C3a anaphylatoxin by radiological contrast agents. Br J Radiol 56: 447–448PubMedGoogle Scholar
  22. Del Balzo UH, Levi R, Polley MJ (1985) Cardiac dysfunction caused by purified human C3a anaphylatoxin. Proc Natl Acad Sci USA 82: 886–890PubMedGoogle Scholar
  23. Del-Balzo UH, Polley MJ, Levi R (1988) Activation of the third complement component (C3) and C3a generation in cardiac anaphylaxis: histamine release and associated inotropic and chronotropic effects. J Pharmacol Exp Ther 246: 911–916PubMedGoogle Scholar
  24. Dias da Silva W, Eisele JW, Lepow IH (1967) Complement as a mediator of inflammation. III. 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’d. J Exp Med 126: 1027–1048Google Scholar
  25. Eaton S, Tsay HM, Yost F, Tweedle M (1987) Effect of iodinated contrast media on a radioimmunoassay of C3a (Abstract). Clin Chem 33: 1470PubMedGoogle Scholar
  26. Erickson BW, Fok K-F, Khan SA, Lukas TJ, Molinar RR, Munoz H, Prystowsky MB, Unson G, Volk-Weiss J, Hugli TE (1981) Synthetic studies of serum complement. In: Rich DH, Gross E (eds) Peptides: synthesis-structure-function. Pierce Chemical, Rockford, IL, pp 525–534Google Scholar
  27. Fernandez HN, Hugli TE (1978) Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. I. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. J Biol Chem 253: 6955–6964PubMedGoogle Scholar
  28. Fukuoka Y, Hugli TE (1986) Degradation of C3a anaphylatoxins by rat mast cells. Fed Proc 45: 381 (Abstract)Google Scholar
  29. Fukuoka Y, Hugli TE (1988) Demonstration of a specific C3a receptor on guinea pig platelets. J Immunol 140: 3496–3501PubMedGoogle Scholar
  30. Gardinali M, Cicardi M, Agostini A, Hugli TE (1987) Complement activation in extracorporeal circulation. Physiological and pathological implications. Pathol Immunopathol Res 5: 352–370Google Scholar
  31. Gerard NP, Hodges MK, Drazen JM, Weller PF, Gerard C (1989a) Characterization of a receptor for C5a anaphylatoxin on human eosinophils. J Biol Chem 264: 1760–1766PubMedGoogle Scholar
  32. Gerard NP, Lively M, Gerard C (1989b) The structure of guinea pig C3a. Mol Immunol 27 (in press)Google Scholar
  33. Gerardy-Schahn R, Ambrosius D, Casaretto M, Grötzinger J, Saunders D, Wollmer A, Brandenburg DM, Bitter-Suermann D (1988) Design and biological activity of a new generation of synthetic C3a analogues by combination of peptidic and non-peptidic elements. Biochem J 255: 209–216PubMedGoogle Scholar
  34. Gervasoni JR Jr, Conrad DH, Hugli TE, Schwartz LB, Ruddy S (1986) Degradation of human anaphylatoxin C3a by rat peritoneal mast cells: a role for the secretory granule enzyme chymase and heparin proteoglycan. J Immunol 136: 285–292PubMedGoogle Scholar
  35. Glovsky MM, Hugli TE, Ishizaka T, Lichtenstein LM, Erickson BW (1979) Anaphylatoxin-induced histamine release with human leucocytes. J Clin Invest 64: 804–811PubMedGoogle Scholar
  36. Gorski JP, Hugli TE, Müller-Eberhard HJ (1979) C4a: The third anaphylatoxin of the human complement system. Proc Natl Acad Sci USA 76: 5299–5302PubMedGoogle Scholar
  37. Greer J (1985) Model structure for the inflammatory protein C5a. Science 228:1055–1060PubMedGoogle Scholar
  38. Haeffner-Cavaillon N, Cavaillon JM, Laude M, Kazatchkine MD (1987) C3a (C3a des Arg) induces production and release of interleukin 1 by cultured human monocytes. J Immunol 139: 794–799PubMedGoogle Scholar
  39. Hartung H-P, Bitter-Suermann D, Hadding U (1983) Induction of thromboxane release from macrophages by anaphylatoxic peptide C3a of complement and synthetic hexapeptide C3a 72–77. J Immunol 130: 1345–1349PubMedGoogle Scholar
  40. Härtung HP, Schwenke C, Bitter-Suermann D, Toyka KV (1987) Guillain-Barré syndrome: activated complement components C3a and C5a in CSF. Neurology 37: 1006–1009PubMedGoogle Scholar
  41. Heidemann M, Hugli TE (1984) Anaphylatoxin generation in multisystem organ failure. J Trauma 24: 1038–1043Google Scholar
  42. Hermann E, Vogt P, Hagmann W, Dunky A, Müller W (1988) Synoviaspiegel von Interleucin-1 und C3a bei chronischer Polyarthritis, Psoriasisarthritis und aktivierter Arthrose. Z Rheumatol 47: 20–25PubMedGoogle Scholar
  43. Herrscher R, Hugli TE, Sullivan TJ (1986) Anaphylatoxin C3a induced mediator relese from mast cells. Fed Proc 45: 243 (Abstract)Google Scholar
  44. Hoeprich PD, Hugli TE (1986) Helical conformation at the carboxyl-terminal portion of human C3a is required for full activity. Biochemistry 25: 1945–1950PubMedGoogle Scholar
  45. Hoffmann T, Böttger C, Baum HP, Messner M, Hadding U, Bitter-Suermann D (1988) In vivo effects of C3a on neutrophils and its contribution to inflammatory lung processes in a guinea-pig model. Clin Exp Immunol 71: 486–492PubMedGoogle Scholar
  46. Huber R, Scholze H, Paques EP, Deisenhofer J (1980) Crystal structure analysis and molecular model of human C3a anaphylatoxin. Hoppe-Seylers Z Physiol Chem 361: 1389–1399PubMedGoogle Scholar
  47. Huey R, Hugli TE (1987) Characterization of the chemotactic C5a receptor on human neutrophils. In: Disabato G (ed) Methods in enzymology, vol 150. Academic, New York, pp 615–627Google Scholar
  48. Huey R, Bloor CM, Kawahara MC, Hugli TE (1983) Potentiation of the anaphylatoxins in vivo using an inhibitor of serum carboxypeptidase N (SCPN). I. Lethality and effects of pulmonary tissue. Am J Pathol 112: 48–60PubMedGoogle Scholar
  49. Huey R, Erickson BW, Bloor CM, Hugli TE (1984a) Concentration of guinea pig lung by synthetic oligopeptide related to human C3a. Immunopharmacology 8: 37–45PubMedGoogle Scholar
  50. Huey R, Bloor CM, Hugli TE (1984b) Effects of human anaphylatoxins on guinea pig atria. Immunopharmacology 8: 147–154PubMedGoogle Scholar
  51. Huey R, Fukuoka Y, Hoeprich PD, Hugli TE (1986) Cellular receptors to the anaphylatoxins C3a and C5a. Biochem Soc Symp 51: 69–81PubMedGoogle Scholar
  52. Hugli TE (1975) Human anaphylatoxin (C3a) from the third component of complement: primary structure. J Biol Chem 250: 8293–8301PubMedGoogle Scholar
  53. Hugli TE (1978) Chemical aspects of the serum anaphylatoxins. In: Reisfeld RA, Inman FP (eds) Contemporary topics in molecular immunology, vol 7. Plenum, New York, pp 181–214Google Scholar
  54. Hugli TE (1981) The structural basis for anaphylatoxin in chemotactic functions of C3a and C5a. CRC Crit Rev Immunol 1(4): 3231–3366Google Scholar
  55. Hugli TE (1984) Structure and function of the anaphylatoxins. Springer Semin Immunopathol 7: 193–219Google Scholar
  56. Hugli TE (1986) Biochemistry and biology of anaphylatoxins. Complement 3: 111–127PubMedGoogle Scholar
  57. Hugli TE, Chenoweth DE (1981) Biologically active peptides of complement: techniques and significance of C3a and C5a measurements. In: Nakamura RM, Dito WR, Tucker ES III (eds), Immunoassays: clinical laboratory techniques for the 1980s, vol 4. Liss, New York, pp 443–460Google Scholar
  58. Hugli TE, Erickson BW (1977) Synthetic peptides with the biological activities and specificity of human C3a anaphylatoxin. Proc Natl Acad Sci USA 74: 1826–1830PubMedGoogle Scholar
  59. Hugli TE, Müller-Eberhard HJ (1978) Anaphylatoxins: C3a and C5a. In: Kunkel HG, Dixon FG (eds) Advances in immunology, vol 26. Academic, New York, pp 1–53Google Scholar
  60. Hugli TE, Morgan WT, Müller-Eberhard HJ (1975a) Circular dichroism of C3a anaphylatoxin: effects of pH, heat, guanidinum chloride and mercaptoethanol on conformation and function. J Biol Chem 250: 1479–1483PubMedGoogle Scholar
  61. Hugli TE, Vallota EH, Müller-Eberhard HJ (1975b) Purification and partial characterization of human and porcine C3a anaphylatoxin. J Biol Chem 250: 1472–1478PubMedGoogle Scholar
  62. Hugli TE, Kawahara MS, Unson CG, Molinor RL, Erickson BW (1983) The active site of human C4a anaphylatoxins. Mol Immunol 20: 637–645PubMedGoogle Scholar
  63. Ivanovich P, Hammerschmidt DE, Chenoweth D, Klinkmann H, Vidovic D (1985) Blood-membrane interaction: C3a, an indicator of biocompatibility. Life Support Syst 3:394–403PubMedGoogle Scholar
  64. Jacobs JW, Rubin JS, Hugli TE, Bogardt RA, Mariz IK, Daniels JS, Daughaday WH, Bradshaw RA (1978) Purification, characterization, and amino acid sequence of rat anaphylatoxin (C3a). Biochemistry 17: 5031–5038PubMedGoogle Scholar
  65. Johnson AR, Hugli TE, Müller-Eberhard HJ (1975) Release of histamine from rat mast cells by the complement peptides C3a and C5a. Immunology 28: 1067–1080PubMedGoogle Scholar
  66. José PJ, Forrest MJ, William TJ (1981) Human C5adesArg increases vascular permeability. J Immunol 127: 2376–2380PubMedGoogle Scholar
  67. Kapp A, Meske-Brand S, Maly FE, Muller W (1984) Complement activation in patients with chronic polyarthritis measured by the level of complement fraction C3a in plasma. Z Rheumatol 43: 103–105PubMedGoogle Scholar
  68. Kapp A, Wokalek H, Schöpf E (1985) Involvement of complement in psoriasis and atopic dermatitis—measurement of C3a and C5a, C3, C4 and C1 inactivator. Arch Dermatol Res 277: 359–361PubMedGoogle Scholar
  69. Ketai LH, Grum CM (1986) C3a and adult respiratory distress syndrome after massive transfusion. Crit Care Med 14: 1001–1003PubMedGoogle Scholar
  70. Kihira Y, Kuratomi Y, Matsuoka R, Kitamura S (1987) Cigarette smoking and lung metabolism — effects of complement C3a and C5a in rabbits. J Thorac Dis (Japan) 25: 643–648Google Scholar
  71. Klos A, Ihring V, Messer M, Grabbe J, Bitter-Suermann D (1988) Detection of native human complement compoennt C3 and C5a and their primary activation peptide C3a and C5a anaphylatoxic peptides by ELISA with monclonal antibodies. J Immunol Methods 111: 241–252PubMedGoogle Scholar
  72. Lamche HR, Paul E, Schlag G, Redl H, Hammerschmidt DE (1988) Development of a simple radioimmunoassay for human C3a. Inflammation 12: 265–276PubMedGoogle Scholar
  73. Langone JJ, Das C, Bennett D, Terman DS (1984) Generation of human C3a, C4a and C5a anaphylatoxins by protein A of Staphylococcus aureu. and immobilized protein A reagents used in serotherapy of cancer. J Immunol 133: 1057–1063PubMedGoogle Scholar
  74. Lepow IH, Kretschmer KW, Patrick RA, Rosen FA (1970) Gross and ultrastructural observations on lesions produced by intradermal injection of human C3a in man. Am J Pathol 61:13–24PubMedGoogle Scholar
  75. Lu ZX, Fok KF, Erickson BW, Hugli TE (1984) Conformation analysis of COOH-terminal fragments of human C3a: evidence of ordered conformation in an active monosapeptide. J Biol Chem 259: 7367–7370PubMedGoogle Scholar
  76. Mahler F, Intaglietta M, Hugli TE, Johnson AR (1975) Influences of C3a anaphylatoxin compared to other vasoactive agents on the microcirculation of the rabbit omentum. Micro vase Res 9: 345–356Google Scholar
  77. Maunder RJ, Harlan JM, Talucci RC, Stager MA, Reed RL, Pep, PE, Hudson LD (1984) Measurement of C3a and C5a in high-risk patients does not predict ARDS. Am Rev Respir Dis 129: A104Google Scholar
  78. Marceau FM, Hugli TE (1984) Effect of C3a and C5a anaphylatoxins on guinea pig isolated blood vessels. J Pharmacol Exp Ther 230: 749–754PubMedGoogle Scholar
  79. Marceau F, Lundberg C, Hugli TE (1987) Effect of the anaphylatoxins on circulation. (Short review). Immunopharmacology 14: 67–84PubMedGoogle Scholar
  80. Marom Z, Shelhamer J, Berger M, Frank M, Kaliner M (1985) Anaphylatoxin C3a enhances mucous glycoprotein release from human airways in vitro. J Exp Med 161: 657–668PubMedGoogle Scholar
  81. Meuer S, Ecker U, Hadding U, Bitter-Suermann D (1981) Platelet-serotonin release by C3a and C5a: two independent pathways of activation. J Immunol 126: 1506–1509PubMedGoogle Scholar
  82. Morgan EL (1987) The role of prostaglandins in C3a-mediated suppression of human in vitro polyclonal antibody response. Clin Immunol Immunopathol 44: 1–11PubMedGoogle Scholar
  83. Morgan EL, Weigle WO, Hugli TE (1982) Anaphylatoxin-mediated regulation of the immune response. I. C3a-mediated suppression of human and murine humoral immune responses. J Exp Med 155: 1412–1426PubMedGoogle Scholar
  84. Morgan EL, Weigle WO, Erickson BW, Fok K-F, Hugli TE (1983) Suppression of humoral immune responses by synthetic C3a peptides. J Immunol 131: 2258–2261PubMedGoogle Scholar
  85. Morgan EL, Thoman ML, Weigle WO, Hugli TE (1985a) Human C3a-mediated suppression of the immune response. I. Suppression of murine in vitro antibody responses occurs through the generation of nonspecific Lyt-2 suppressor T cell. J Immunol 134: 51–57PubMedGoogle Scholar
  86. Morgan EL, Thoman ML, Hobbs MV, Weigle WO, Hugli TE (1985b) Human C3a-mediated suppression of the immune response. II. Suppression of human in vitro polyclonal antibody responses occurs through the generation of nonspecific OKT8+ suppressor T cells. Clin Immunol Immunopathol 37: 114–123PubMedGoogle Scholar
  87. Muto Y, Fukumoto Y, Arata Y (1985) Proton nuclear magnetic resonance study of the third component of complement: solution conformation of the carboxyl-terminal segment of C3a fragment. Biochemistry 24: 6659–6665PubMedGoogle Scholar
  88. Nagata S, Glovsky MM (1987) Activation of human serum complement with allergens. J Allergy Clin Immunol 80: 24–32PubMedGoogle Scholar
  89. Needleman BW, Weiler JM, Feldbush TL (1981) The third component of complement inhibits human lymphocyte blastogenesis. J Immunol 125: 1586–1589Google Scholar
  90. Nehesheim DG, Edalji RP, Mollison KW, Greer J, Zuiderweg RP (1988) Secondary structure of complement component C3a anaphylatoxins in solution as determined by NMR spectroscopy: differences between crystal and solution conformations. Proc Natl Acad Sci USA 85: 5036–5040Google Scholar
  91. Nilsson B, Svensson KE, Inganäs M, Nilsson UR (1988) A simplified assay for the detection of C3a in human plasma employing a monoclonal antibody raised against denatured C3. J Immunol Methods 107: 281–287PubMedGoogle Scholar
  92. Ohkohchi K, Takematsu H, Tagami H (1985) Increased anaphylatoxins (C3a and C4a) in psoriatic sera. Br J Dermatol 113: 189–196PubMedGoogle Scholar
  93. Paques E, Scholze H, Huber R (1980) Purification and crystallization of human anaphylatoxin C3a. Hoppe-Seylers Z Physiol Chem 361: 977–980PubMedGoogle Scholar
  94. Payan DG, Trenthan DE, Goetzl EG (1982) Modulation of human lymphocyte function by C3a and C3a (70–77). J Exp Med 156: 756–765PubMedGoogle Scholar
  95. Polley MJ, Nachman RL (1983) Human platelet activation by C3a and C3a des arg. J Exp Med 158: 603–615PubMedGoogle Scholar
  96. Satoh PS, Yonker TC, Kane DP, Yeagley BW (1983) Measurement of anaphylatoxins: an index for activation of complement cascades (1983) Biotechniques 1: 90–95Google Scholar
  97. Schupf N, Williams CA, Cox J, Hugli TE, (1983) Psycho-pharmacological activity of anaphylatoxin C3a in rat hypothalamus. J Neuroimmunol 5: 305–316PubMedGoogle Scholar
  98. Schwartz LB, Kawahara MS, Hugli TE, Fearon DT, Austen KF (1983) Generation of C3a anaphylatoxin from human C3 by human mast cell trypstase. J Immunol 130:1891–1895PubMedGoogle Scholar
  99. Spencer PC, Schmidt B, Gurland HJ (1986) Determination of plasma C3a des Arg levels after blood contact with foreign surfaces. Artif Organs 10: 61–63PubMedGoogle Scholar
  100. Stegemann H, Vogt W, Friedberg KD (1964) Über die Natur des Anaphylatoxins. Hoppe-Seylers Z Physiol Chem 337: 269–276PubMedGoogle Scholar
  101. Stimler NP, Hugli TE, Bloor CM (1980) Pulmonary injury induced by C3a and C5a anaphylatoxins. Am J Pathol 100: 327–340PubMedGoogle Scholar
  102. Stimler NP, Brockelhurst WE, Hugli TE, Bloor CM (1981) Anaphylatoxin mediated contraction of guinea pig lung strips: a non-histamine tissue response. J Immunol 126:2258–2261PubMedGoogle Scholar
  103. Stimler NP, Bloor CM, Hugli TE (1983) C3a-induced contraction of guinea pig lung parenchymal: role of cyclooxygenase metabolites. Immunopharmacology 5: 251–257PubMedGoogle Scholar
  104. Strunk RC, Webster RO (1985) Inhibition of cleavage of the third component of human complement (C3) by its small cleavage fragment C3a: inhibition occurs with the classical-pathway, but not the alternative-pathway, C3 convertase. Mol Immunol 22: 37–43PubMedGoogle Scholar
  105. Suzuki Y, Uchida J, Tsuji H, Kuzuhara K, Hara S, Nihei H, Ogura Y, Otsubo O, Mimura, N. (1987) Acute changes in C3a in an anaphylactoid reaction in hemodialysis patients. Tohoku J Exp Med 152(1): 35–45PubMedGoogle Scholar
  106. Takematsu H, Ohkohchi K, Tagami H (1986) Demonstration of anaphylatoxins C3a, C4a and C5a in the scales of psoriasis and inflammatory pustular dermatoses. Br J Dermatol 114:1–6PubMedGoogle Scholar
  107. Unson CG, Erickson BW, Hugli TE (1984) Active site of C3a anaphylatoxin: contributions of the lipophilic and orienting residues. Biochemistry 23: 585–589PubMedGoogle Scholar
  108. Vallota EH, Müller-Eberhard HJ (1973) Isolation and characterization of a new and highly active form of C5a anaphylatoxin from epsilon-aminocapric acid-containing porcine serum. J Exp Med 137: 1109–1123PubMedGoogle Scholar
  109. Wagner JL, Hugli TE (1984) Radioimmunoassay for anaphylatoxins in biological fluids: a sensitive method for determining complement activation. Anal Biochem 136: 75–88PubMedGoogle Scholar
  110. Watson JW, Drazen JM, Stimler-Gerard NP (1988) Synergism between inflammatory mediators in vivo. Am Rev Respir Dis 137: 636–640PubMedGoogle Scholar
  111. Weigle WO, Goodman MG, Morgan EL, Hugli TE (1983) Regulation of immune response by fragments of the C3 components of complemnt. Springer Semin Immunopathol 6:173–194Google Scholar
  112. Westaby S, Dawson P, Turner MW, Pridie RB (1985) Angiography and complement activation. Evidence for generation of C3a anaphylatoxins by intravascular contrast agents. Cardiovas Res 19: 85–88Google Scholar
  113. Wetsel RA, Lundwall A, Davidson F, Gibson T, Tack BF, Fey GH (1984) Structure of murine complement component C3. J Biol Chem 259: 13857–13862PubMedGoogle Scholar
  114. Wuepper RB, Bokisch VA, Müller-Eberhard HJ, Stoughton RB (1972) Cutaneous responses to human C3 anaphylatoxin. Clin Exp Immunol 11: 13–20PubMedGoogle Scholar
  115. Zanker B, Rasokat H, Hadding U, Bitter-Suermann D (1982) C3a induced activation and stimulus specific reversible densitization of guinea pig platelets. Agents Action [Suppl] 11: 147–157Google Scholar
  116. Zuiderweg ERP, Mollison KW, Henkin J, Carter GW (1988) Sequence-specific assignments in the 1H NMR spectrum of the human inflammatory protein C5a. Biochemistry 27:3568–3580PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • T. E. Hugli
    • 1
  1. 1.Department of ImmunologyResearch Institute of Scripps ClinicLa JollaUSA

Personalised recommendations