Skip to main content
SpringerLink
Log in

Sequence, evolution and ligand binding properties of mammalian Duffy antigen/receptor for chemokines

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The Duffy antigen/receptor for chemokine, DARC, acts as a widely expressed promiscuous chemokine receptor and as the erythrocyte receptor for Plasmodium vivax. To gain insight into the evolution and structure/function relations of DARC, we analyzed the binding of anti-human Fy monoclonal antibodies (mAbs) and human chemokines to red blood cells (RBCs) from 11 nonhuman primates and two nonprimate mammals, and we elucidated the structures of the DARC genes from gorilla, gibbon, baboon, marmoset, tamarin, night monkey and cattle. CXCL-8 and CCL-5 chemokine binding analysis indicated that the promiscuous binding profile characteristic of DARC is conserved across species. Among three mAbs that detected the Fy6 epitope by flow cytometric analysis of human and chimpanzee RBCs, only one reacted with night monkey and squirrel monkey. Only chimpanzee RBCs bound a significant amount of the anti-Fy3 mAb. Fy3 was also poorly detected on RBCs from gorilla, baboon and rhesus monkey, but not from new world monkeys. Alignment of DARC homologous sequences allowed us to construct a phylogenetic tree in which all branchings were in accordance with current knowledge of primate phylogeny. Although DARC was expected to be under strong internal and external selection pressure, in order to maintain chemokine binding and avoid Plasmodium vivax binding, respectively, our present study did not provide arguments in favor of a selection pressure on the extracellular domains involved in ligand specificity. The amino acid variability of DARC-like polypeptides was found to be well correlated with the hydrophylicity indexes, with the highest divergence on the amino-terminal extracellular domain. Analysis of the deduced amino acid sequences highlighted the conservation of some amino acid residues, which should prove to be critical for the structural and functional properties of DARC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1a, b
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alvarez V, Coto E, Setien F, Gonzalez S, Gonzalez-Roces S, Lopez-Larrea C (1996) Characterization of interleukin-8 receptors in nonhuman primates. Immunogenetics 43:261–267

    Article  CAS  PubMed  Google Scholar 

  • Blancher A, Reid ME, Socha WW (2000) Cross-reactivity of antibodies to human and primate red cell antigens. Transfus Med Rev 14:161–179

    CAS  PubMed  Google Scholar 

  • Chaudhuri A, Pogo AO (1995) The Duffy blood group system and malaria. In: Cartron JP, Rouger P (eds) Blood cell biochemistry, vol 6. Plenum Press, New York, pp 243–265

  • Chaudhuri A, Polyakova J, Zbrzezna V, Pogo OA (1995) The coding sequence of Duffy blood group gene in human and simians: restriction fragment length polymorphism, antibody and malaria specificities, and expression in nonerythroid tissues in Duffy-negative individuals. Blood 85:615–1995

    CAS  PubMed  Google Scholar 

  • Chaudhuri A, Nielsen S, Elkjaer ML, Zbrzezna V, Fang F, Pogo OA (1997) Detection of Duffy antigen in the plasma membranes and caveolae of vascular endothelial and epithelial cells of nonerythroid organs. Blood 89:701–712

    CAS  PubMed  Google Scholar 

  • Chitnis CE, Chaudhuri A, Horuk R, Pogo OA, Miller LH (1996) The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasites to erythrocytes. J Exp Med 184:1531–1536

    CAS  PubMed  Google Scholar 

  • Darbonne WC, Rice GC, Mohler MA, Apple T, Hebert CA, Valente AJ, Baker JB (1991) Red blood cells as sink for interleukin-8, a leukocyte chemotaxin. J Clin Invest 88:1362–1369

    CAS  PubMed  Google Scholar 

  • Dawson TC, Lentsch AB, Wang Z, Cowhig JE, Rot A, Maeda N, Peiper SC. (2000) Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). Blood 96:1681–1684

    CAS  PubMed  Google Scholar 

  • Hadley TJ, Lu ZH, Wasniowska K, Martin AW, Peiper SC, Hesselgesser J, Horuk R (1994) Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform. J Clin Invest 88:985–991

    Google Scholar 

  • Horuk R (1994) Molecular properties of the chemokine receptor family. Trends Pharmacol Sci 15:159–165

    Article  CAS  PubMed  Google Scholar 

  • Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, Miller L (1993) A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science 261:1182–1183

    CAS  PubMed  Google Scholar 

  • Horuk R, Zi-xuan W, Peiper SC, Hesselgessr J (1994) Identification and characterization of a promiscuous chemokine-binding protein in a human erythroleukemic cell line. J Biol Chem 269:17730–17733

    CAS  PubMed  Google Scholar 

  • Horuk R, Martin A, Hesselgesser J, Hadley T, Lu ZH, Wang ZX, Peiper SC (1996) The Duffy antigen receptor for chemokines: structural analysis and expression in the brain. J Leukoc Biol 59:29–38

    CAS  PubMed  Google Scholar 

  • Huang CH, Liu Z, Apoil PA, Blancher A (2000) Sequence, organization, and evolution of Rh50 glycoprotein genes in nonhuman primates. J Mol Evol 51:76–87

    CAS  PubMed  Google Scholar 

  • Iwamoto S, Omi T, Kajii E, Ikemoto S (1995) Genomic organization of the glycoprotein D gene: Duffy blood group Fya/Fyb alloantigen system is associated with a polymorphism at the 44-amino acid residue. Blood 85:622–625

    CAS  PubMed  Google Scholar 

  • Kimura MA (1980) Simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16:111–120

    PubMed  Google Scholar 

  • Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132

    CAS  PubMed  Google Scholar 

  • Kumar S, Tamura K, Nei M (1993) MEGA: Molecular Evolution Genetics Analysis (version 1.01). The Pennsylvania State University, University Park, Penn.

  • Lee JS, Frevert CW, Wurfel MM, Peiper SC, Wong VA, Ballman KK, Ruzinski JT, Rhim JS, Martin TR, Goodman RB (2003) Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. J Immunol 170:5244–5251

    CAS  PubMed  Google Scholar 

  • Lentsch AB (2002) The Duffy antigen/receptor for chemokines (DARC) and prostate cancer. A role as clear as black and white? FASEB J 16:1093–1095

    Article  CAS  PubMed  Google Scholar 

  • Leong SR, Kabakoff RC, Hebert CA (1994) Complete mutagenesis of the extracellular domain of interleukin-8 (IL-8) type A receptor identifies charged residues mediating Il-8 binding and signal transduction. J Biol Chem 269:19343–19348

    CAS  PubMed  Google Scholar 

  • Liu XH, Hadley TJ, Xu L, Peiper SC, Ray PE (1999) Up-regulation of Duffy antigen receptor expression in children with renal disease. Kidney Int 55:1491–1500

    Article  CAS  PubMed  Google Scholar 

  • Lu ZH, Wang ZX, Horuk R, Hesselgesser J, Yan-chun L, Hadley TJ, Peiper SC (1995) The promiscuous chemokine binding profile of the Duffy Antigen/Receptor for Chemokines is primarily localised to sequences in the amino-terminal domain. J Biol Chem 270:26239–26245

    Article  CAS  PubMed  Google Scholar 

  • Luo H, Chaudhuri A, Johnson KR, Neote K, Zbrzezna V, He Y, Pogo AO (1997) Cloning, characterization, and mapping of a murine promiscuous chemokine receptor gene: homolog of the human Duffy gene. Genome Res 7:932–941

    CAS  PubMed  Google Scholar 

  • Luo H, Chaudhuri A, Zbrzezna V, He Y, Pogo AO (2000) Deletion of the murine Duffy gene (Dfy) reveals that the Duffy receptor is functionally redundant. Mol Cell Biol 20:3097–3101

    Article  CAS  PubMed  Google Scholar 

  • Mallinson G, Soo KS, Schall TJ, Pisacka M, Anstee DJ (1995) Mutations in the erythrocyte chemokine receptor (Duffy) gene : the molecular basis of the Fya/Fyb antigens and identification of a deletion in the Duffy gene of an apparently healthy individual with the Fy(a−b−) phenotype. Br J Haematol 90:823–829

    CAS  PubMed  Google Scholar 

  • Miller LH, Mason SJ, Dvorack JA, McGinnis MH, Rothman KI (1975) Erythrocyte receptors for (Plasmodium knowlesi) malaria: Duffy blood group determinants. Science 189:561–563

    CAS  PubMed  Google Scholar 

  • Miller LH, Mason SJ, Clyde DF, McGinnis MH (1976) The resistance factor to Plasmodium vivax in blacks. N Engl J Med 295:302–305

    CAS  PubMed  Google Scholar 

  • Murphy PM (2000) Chemokine receptor cloning. Methods Mol Biol 138:89–98

    Article  CAS  PubMed  Google Scholar 

  • Neote K, Mak JY, Kolakowski LF, Schall TJ (1994) Functional and biochemical analysis of the cloned Duffy antigen: identity with the red blood cell chemokine factor. Blood 84:44–52

    CAS  PubMed  Google Scholar 

  • Nichols ME, Rubinstein P, Barnwell J, Rodriguez de Cordoba S, Rosenfield R (1987) A new human blood group specificity define by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax. J Exp Med 166:776–785

    CAS  PubMed  Google Scholar 

  • Palatnik M, Rowe AW (1984) Duffy and Duffy-related human antigens in primates. J Hum Evol 13:173–179

    Google Scholar 

  • Patterson AM, Schmutz C, Davis S, Gardner L, Ashton BA, Middleton J (2002) Differential binding of chemokines to macrophages and neutrophils in the human inflamed synovium. Arthritis Res 4:209–214

    Article  CAS  PubMed  Google Scholar 

  • Peiper SC, Wang Z, Neote K, Martin AW, Showel AJ, Conklyn MJ, Ogborne K, Hadley TJ, Lu ZH, Hesselgesser J, Horuk R (1995) The Duffy Antigen/Receptor for Chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. J Exp Med 81–1311–1317

  • Probst WC, Snyder LA, Schuster DI, Brosius J, Sealfon SC (1992) Sequence alignment of the G-protein coupled receptor superfamily. DNA Cell Biol 11:1–20

    CAS  PubMed  Google Scholar 

  • Riwom S, Janvier D, Navenot JM, Benbunan M, Muller JY, Blanchard D (1994) Production of a new murine monoclonal antibody with Fy6 specificity and characterization of the immunopurified N-glycosylated Duffy-active molecule. Vox Sang 66:61–67

    CAS  PubMed  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    CAS  PubMed  Google Scholar 

  • Segerer S, Regele H, MacK M, Kain R, Cartron JP, Colin Y, Kerjaschki D, Schlondorff D (2000) The Duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis. Kidney Int 58:1546–1556

    Article  CAS  PubMed  Google Scholar 

  • Segerer S, Cui Y, Eitner F, Goodpaster T, Hudkins KL, Mack M, Cartron JP, Colin Y, Schlondorff D, Alpers CE (2001) Expression of chemokines and chemokine receptors during human renal transplant rejection. Am J Kidney Dis 37:518–531

    CAS  PubMed  Google Scholar 

  • Segerer S, Böhmig GA, Exner M, Colin Y, Cartron JP, Kerjaschki D, Schlondorff D, Regele H (2003) When renal allografts turn DARC. Transplantation 75:1030–1034

    PubMed  Google Scholar 

  • Seixas S, Ferrand N, Rocha J (2002) Microsatellite variation and evolution of the human Duffy blood group polymorphism. Mol Biol Evol 19:1802–1806

    CAS  PubMed  Google Scholar 

  • Shakin-Eshleman SH, Spitalnik SL (1993) Role of individual N-linked glycans in cell surface expression and secretion of glycoproteins. Trends Glycosci Glycotechnol 5:355–368

    CAS  Google Scholar 

  • Socha WW, Lasano SG (1997) Monoclonal antibodies against human blood group related antigens in tests with non-human primate red cells. Transfus Clin Biol. 4:111–114

  • Szabo MC, Soo KS, Zlotnik A, Schall TJ (1995) Chemokine class differences in binding to the Duffy antigen-erythrocyte chemokine receptor. J Biol Chem 270:25348–25351

    Article  CAS  PubMed  Google Scholar 

  • Tang T, Owen JD, Du J, Walker CL, Richmond A (1998) Molecular cloning and characterization of a mouse gene with homology to the Duffy-antigen receptor for chemokines. DNA Seq 9:129–143

    CAS  PubMed  Google Scholar 

  • Thompson JD, Higgins DJ, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choices. Nucleic Acids Res 22:4673–4680

    PubMed  Google Scholar 

  • Tournamille C, Le Van Kim C, Gane P, Cartron JP, Colin Y (1995a) Molecular basis and PCR-DNA typing of the Fya/Fyb blood group polymorphism. Hum Genet 95:407–410

    CAS  PubMed  Google Scholar 

  • Tournamille C, Colin Y, Cartron JP, Le Van Kim C (1995b) Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet 10:224–228

    CAS  PubMed  Google Scholar 

  • Tournamille C, Le Van Kim C, Gane P, Blanchard D, Proudfoot AE, Cartron JP, Colin Y (1997) Close association of the first and fourth extracellular domains of the Duffy antigen/receptor for chemokines by a disulphide bond is required for ligand binding. J Biol Chem 272:16274–16280

    Article  CAS  PubMed  Google Scholar 

  • TournamilleC, FilipeA, WasniowskaK, GaneP, LisowskaE, CartronJP, ColinY, Le Van KimC (2003) Structure/function analysis of the extracellular domains of the Duffy Antigen/Receptor for Chemokines : characterization of antibody and chemokine binding sites. Br J Haematol 122:1014–1023

    Article  CAS  PubMed  Google Scholar 

  • Varki A (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97–130

    CAS  PubMed  Google Scholar 

  • Wasniowska K, Eicchenberger P, Kugele F, Hadley TJ (1993) Purification of a 28-kD non-aggregating tryptic peptide of the Duffy blood group protein. Biochem Biophys Res Commun 192:366–372

    Article  CAS  PubMed  Google Scholar 

  • Wasniowska K, Blanchard D, Janvier D, Wang ZX, Peiper SC, Hadley TJ, Lisowska E (1996) Identification of the Fy6 epitope recognized by two monoclonal antibodies in the N-terminal extracellular portion of the Duffy antigen receptor for chemokines. Mol Immunol 33:917–923

    Article  CAS  PubMed  Google Scholar 

  • Wasniowska K, Czerwinski M, Jachymek W, Lisowska E (2000a) Expression and binding properties of a soluble chimeric protein containing the N-terminal domain of the Duffy antigen. Biochem Biophys Res Commun 273:705–711

    Article  CAS  PubMed  Google Scholar 

  • Wasniowska K, Tournamille C, Le Van Kim C, Buffiere J, Uschikawa M, Blanchard D, Lisowska E, Cartron JP, Colin Y (2000b) Characterization of the FYA and FYB epitopes recognized by monoclonal antibodies on the Duffy Receptor/Antigen for Chemokines (abstract). Vox Sang 78:29

    PubMed  Google Scholar 

  • Wasniowska K, Petit-LeRoux Y, Tournamille C, Le Van Kim C, Cartron JP, Colin Y, Lisowska E, Blanchard D (2002) Structural characterization of the epitope recognized by the new anti-Fy6 monoclonal antibody NaM185-2C3. Transfus Med 12:205–211

    Article  CAS  PubMed  Google Scholar 

  • Wertheimer SP, Barnwell JW (1989) Plasmodium vivax interaction with the human Duffy blood group glycoprotein: identification of a parasite receptor-like protein. Exp Parasitol 69:340–350

    CAS  PubMed  Google Scholar 

  • Yang Z (1995) Phylogenetic analysis by maximum likelihood (PAML), version 1.4. University College, London

  • Zhang J, Rosenberg HF, Nei M (1998) Positive Darwinian selection after gene duplication in primate ribonuclease genes. Proc Natl Acad Sci USA 95:3708–3713

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM U76, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015, Paris, France

    Christophe Tournamille, Caroline Le Van Kim, Pierre Gane, Jean Pierre Cartron & Yves Colin

  2. Laboratoire d’Immunologie Moléculaire, Université Paul Sabatier, Immunologie, Hôpital Rangueil, Avenue Jean Poulhes, TSA 30030, 31059 , Toulouse, Cedex, France

    Antoine Blancher & Pol André Apoil

  3. Universidade Estadual Paulista, Botucatu, Brasil

    Wilson Nakamoto

Authors
  1. Christophe Tournamille
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antoine Blancher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caroline Le Van Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pierre Gane
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pol André Apoil
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wilson Nakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jean Pierre Cartron
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yves Colin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yves Colin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tournamille, C., Blancher, A., Le Van Kim, C. et al. Sequence, evolution and ligand binding properties of mammalian Duffy antigen/receptor for chemokines. Immunogenetics 55, 682–694 (2004). https://doi.org/10.1007/s00251-003-0633-2

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-003-0633-2

Keywords

Search

Navigation