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Immunology. Aug 1994; 82(4): 516–521.
PMCID: PMC1414921

Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors.


The C5a anaphylatoxin is a potent complement-derived mediator of inflammation with chemotactic activity. In this study the possible role of specific high-affinity binding sites for C5a on peripheral blood leucocytes for the removal of C5a from human blood plasma was investigated. The addition of purified granulocytes or mononuclear cells to complement-activated plasma resulted in the rapid and dose-dependent removal of up to 80% of plasma C5a, as determined by ELISA. The specific role of leucocyte C5a receptors (C5aR) in the plasma clearance of C5a was demonstrated by the inhibition of C5a uptake by the preincubation of cells with the C5aR-specific monoclonal antibody S5/1. Furthermore, U937 cells which had been induced by db-cAMP to express C5aR, but not undifferentiated U937 cells, were capable of removing C5a from plasma. The inhibition of C5aR internalization by monensin did not affect C5a uptake by leucocytes. The co-incubation with leucocytes had no effect on the plasma clearance of complement activation products C3a or terminal complement complex (TCC), as determined by this in vitro assay. The binding of the C5a anaphylatoxin to cellular receptors represents an effective control mechanism that protects the organism from systemic effects of this potent phlogistic mediator.

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Selected References

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  • Tardif M, Mery L, Brouchon L, Boulay F. Agonist-dependent phosphorylation of N-formylpeptide and activation peptide from the fifth component of C (C5a) chemoattractant receptors in differentiated HL60 cells. J Immunol. 1993 Apr 15;150(8 Pt 1):3534–3545. [PubMed]
  • Bokisch VA, Müller-Eberhard HJ. Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase. J Clin Invest. 1970 Dec;49(12):2427–2436. [PMC free article] [PubMed]
  • Swerlick RA, Yancey KB, Lawley TJ. A direct in vivo comparison of the inflammatory properties of human C5a and C5a des Arg in human skin. J Immunol. 1988 Apr 1;140(7):2376–2381. [PubMed]
  • Weisdorf DJ, Hammerschmidt DE, Jacob HS, Craddock PR. Rapid in vivo clearance of C5ades arg: a possible protective mechanism against complement-mediated tissue injury. J Lab Clin Med. 1981 Dec;98(6):823–830. [PubMed]
  • Webster RO, Larsen GL, Henson PM. In vivo clearance and tissue distribution of C5a and C5a des arginine complement fragments in rabbits. J Clin Invest. 1982 Dec;70(6):1177–1183. [PMC free article] [PubMed]
  • Huey R, Hugli TE. Characterization of a C5a receptor on human polymorphonuclear leukocytes (PMN). J Immunol. 1985 Sep;135(3):2063–2068. [PubMed]
  • Oppermann M, Raedt U, Hebell T, Schmidt B, Zimmermann B, Götze O. Probing the human receptor for C5a anaphylatoxin with site-directed antibodies. Identification of a potential ligand binding site on the NH2-terminal domain. J Immunol. 1993 Oct 1;151(7):3785–3794. [PubMed]
  • Würzner R, Schulze M, Happe L, Franzke A, Bieber FA, Oppermann M, Götze O. Inhibition of terminal complement complex formation and cell lysis by monoclonal antibodies. Complement Inflamm. 1991;8(5-6):328–340. [PubMed]
  • Oppermann M, Haubitz M, Quentin E, Götze O. Complement activation in patients with renal failure as detected through the quantitation of fragments of the complement proteins C3, C5, and factor B. Klin Wochenschr. 1988 Sep 15;66(18):857–864. [PubMed]
  • Plummer TH, Jr, Ryan TJ. A potent mercapto bi-product analogue inhibitor for human carboxypeptidase N. Biochem Biophys Res Commun. 1981 Jan 30;98(2):448–454. [PubMed]
  • Chenoweth DE. Anaphylatoxin formation in extracorporeal circuits. Complement. 1986;3(3):152–165. [PubMed]
  • Oppermann M, Höpken U, Götze O. Assessment of complement activation in vivo. Immunopharmacology. 1992 Sep-Oct;24(2):119–134. [PubMed]
  • Bingel M, Arndt W, Schulze M, Floege J, Shaldon S, Koch KM, Götze O. Comparative study of C5a plasma levels with different hemodialysis membranes using an enzyme-linked immunosorbent assay. Nephron. 1989;51(3):320–324. [PubMed]
  • Craddock PR, Fehr J, Dalmasso AP, Brighan KL, Jacob HS. Hemodialysis leukopenia. Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes. J Clin Invest. 1977 May;59(5):879–888. [PMC free article] [PubMed]
  • Werfel T, Sonntag G, Weber MH, Götze O. Rapid increases in the membrane expression of neutral endopeptidase (CD10), aminopeptidase N (CD13), tyrosine phosphatase (CD45), and Fc gamma-RIII (CD16) upon stimulation of human peripheral leukocytes with human C5a. J Immunol. 1991 Dec 1;147(11):3909–3914. [PubMed]
  • Jesaitis RK, Dahinden CA, Chang CM, Jesaitis AJ. Investigations on the role of Golgi-mediated, ligand-receptor processing in the activation of granulocytes by chemoattractants: differential effects of monensin. Biochim Biophys Acta. 1987 Mar 11;927(3):382–391. [PubMed]
  • Van Epps DE, Simpson S, Bender JG, Chenoweth DE. Regulation of C5a and formyl peptide receptor expression on human polymorphonuclear leukocytes. J Immunol. 1990 Feb 1;144(3):1062–1068. [PubMed]
  • Van Epps DE, Simpson SJ, Chenoweth DE. C5a and formyl peptide receptor regulation on human monocytes. J Leukoc Biol. 1992 Apr;51(4):393–399. [PubMed]
  • Barker MD, Jose PJ, Williams TJ, Burton DR. The chemoattractant des-Arg74-C5a regulates the expression of its own receptor on a monocyte-like cell line. Biochem J. 1986 Jun 1;236(2):621–624. [PMC free article] [PubMed]
  • Fukuoka Y, Hugli TE. Anaphylatoxin binding and degradation by rat peritoneal mast cells. Mechanisms of degranulation and control. J Immunol. 1990 Sep 15;145(6):1851–1858. [PubMed]
  • Mousli M, Hugli TE, Landry Y, Bronner C. A mechanism of action for anaphylatoxin C3a stimulation of mast cells. J Immunol. 1992 Apr 15;148(8):2456–2461. [PubMed]
  • Klos A, Bank S, Gietz C, Bautsch W, Köhl J, Burg M, Kretzschmar T. C3a receptor on dibutyryl-cAMP-differentiated U937 cells and human neutrophils: the human C3a receptor characterized by functional responses and 125I-C3a binding. Biochemistry. 1992 Nov 24;31(46):11274–11282. [PubMed]
  • Elsner J, Oppermann M, Czech W, Kapp A. C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins. Blood. 1994 Jun 1;83(11):3324–3331. [PubMed]
  • Gerardy-Schahn R, Ambrosius D, Saunders D, Casaretto M, Mittler C, Karwarth G, Görgen S, Bitter-Suermann D. Characterization of C3a receptor-proteins on guinea pig platelets and human polymorphonuclear leukocytes. Eur J Immunol. 1989 Jun;19(6):1095–1102. [PubMed]

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