Advertisement

Inflammation Research

, Volume 58, Issue 8, pp 431–435 | Cite as

Shedding light on DARC: the role of the Duffy antigen/receptor for chemokines in inflammation, infection and malignancy

  • K. Horne
  • Ian J. Woolley
Review

Introduction

Duffy antigen (Fy) was first identified in 1950 as a cause of transfusion reactions [1], and 25 years later recognized as receptor allowing the entry of Plasmodium vivax into erythrocytes [2]. It was not until the mid 1990s that a physiological role for this antigen was proposed, when Duffy was found to be a chemokine receptor [3] and was subsequently renamed Duffy antigen receptor for chemokines (DARC). Since then roles for DARC in inflammation, infection and malignancy have begun to emerge.

Most individuals from Sub-Saharan Africa, or of African descent, have a mutation that prevent DARC expression on erythrocytes, but not other sites of DARC expression, such as endothelial cells. Interest in the clinical and scientific implications of DARC has risen as it has become a potential explanation for some of the differences in prognosis and presentation seen in those with African genealogy in diseases of inflammation and malignancy.

This paper reviews the evidence for DARC...

Keywords

Giant Cell Arteritis Neutrophil Migration Delay Graft Function Vivax Infection Crescentic Glomerulonephritis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Cutbush M, Mollison PL. The Duffy blood group system. Heredity. 1950;4:383–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Miller LH, Mason SJ, Dvorak JA, McGinniss MH, Rothman IK. Erythrocyte receptors for (Plasmodium knowlesi) malaria: Duffy blood group determinants. Science. 1975;189:561–3.PubMedCrossRefGoogle Scholar
  3. 3.
    Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, et al. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science. 1993;261:1182–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Hadley TJ, Peiper SC. From malaria to chemokine receptor: the emerging physiologic role of the Duffy blood group antigen. Blood. 1997;89:3077–91.PubMedGoogle Scholar
  5. 5.
    Gardner L, Patterson AM, Ashton BA, Stone MA, Middleton J. The human Duffy antigen binds selected inflammatory but not homeostatic chemokines. Biochem Biophys Res Commun. 2004;321:306–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Comerford I, Nibbs RJ. Post-translational control of chemokines: a role for decoy receptors? Immunol Lett. 2005;96:163–74.PubMedCrossRefGoogle Scholar
  7. 7.
    Horuk R, Martin A, Hesselgesser J, Hadley T, Lu ZH, Wang ZX, et al. The Duffy antigen receptor for chemokines: structural analysis and expression in the brain. J Leukoc Biol. 1996;59:29–38.PubMedGoogle Scholar
  8. 8.
    Middleton J, Americh L, Gayon R, Julien D, Mansat M, Mansat P, et al. A comparative study of endothelial cell markers expressed in chronically inflamed human tissues: MECA-79, Duffy antigen receptor for chemokines, von Willebrand factor, CD31, CD34, CD105 and CD146. J Pathol. 2005;206:260–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee JS, Frevert CW, Wurfel MM, Peiper SC, Wong VA, Ballman KK, et al. Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. J Immunol. 2003;170:5244–51.PubMedGoogle Scholar
  10. 10.
    Pruenster M, Mudde L, Bombosi P, Dimitrova S, Zsak M, Middleton J, et al. The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity. Nat Immunol. 2009;10:101–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Dawson TC, Lentsch AB, Wang Z, Cowhig JE, Rot A, Maeda N, et al. Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). Blood. 2000;96:1681–4.PubMedGoogle Scholar
  12. 12.
    Luo H, Chaudhuri A, Zbrzezna V, He Y, Pogo AO. Deletion of the murine Duffy gene (Dfy) reveals that the Duffy receptor is functionally redundant. Mol Cell Biol. 2000;20:3097–101.PubMedCrossRefGoogle Scholar
  13. 13.
    Zarbock A, Schmolke M, Bockhorn SG, Scharte M, Buschmann K, Ley K, et al. The Duffy antigen receptor for chemokines in acute renal failure: a facilitator of renal chemokine presentation. Crit Care Med. 2007;35:2156–63.PubMedCrossRefGoogle Scholar
  14. 14.
    Wadhwa M, Seghatchian MJ, Dilger P, Contreras M, Thorpe R. Cytokine accumulation in stored red cell concentrates: effect of buffy-coat removal and leucoreduction. Transfus Sci. 2000;23:7–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Jilma B, Akimitsu N, Fukuma N, Sekimizu K, Jilma-Stohlawetz P. Man, mouse and Duffy genotype-phenotype-specific pharmacokinetics of monocyte chemotactic protein-1. Transfus Med. 2004;14:251–2.PubMedCrossRefGoogle Scholar
  16. 16.
    Smith E, McGettrick HM, Stone MA, Shaw JS, Middleton J, Nash GB, et al. Duffy antigen receptor for chemokines and CXCL5 are essential for the recruitment of neutrophils in a multicellular model of rheumatoid arthritis synovium. Arthritis Rheum. 2008;58:1968–73.PubMedCrossRefGoogle Scholar
  17. 17.
    Akalin E, Neylan JF. The influence of Duffy blood group on renal allograft outcome in African Americans. Transplantation. 2003;75:1496–500.PubMedCrossRefGoogle Scholar
  18. 18.
    Mange KC, Prak EL, Kamoun M, Du Y, Goodman N, Danoff T, et al. Duffy antigen receptor and genetic susceptibility of African Americans to acute rejection and delayed function. Kidney Int. 2004;66:1187–92.PubMedCrossRefGoogle Scholar
  19. 19.
    He W, Neil S, Kulkarni H, Wright E, Agan BK, Marconi VC, et al. Duffy antigen receptor for chemokines mediates trans-infection of HIV-1 from red blood cells to target cells and affects HIV-AIDS susceptibility. Cell Host Microbe. 2008;4:52–62.PubMedCrossRefGoogle Scholar
  20. 20.
    Lachgar A, Jaureguiberry G, Le Buenac H, Bizzini B, Zagury JF, Rappaport J, et al. Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). Biomed Pharmacother. 1998;52:436–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Woolley IJ, Kalayjian R, Valdez H, Hamza N, Jacobs G, Lederman MM, et al. HIV nephropathy and the Duffy antigen/receptor for chemokines in African Americans. J Nephrol. 2001;14:384–7.PubMedGoogle Scholar
  22. 22.
    Velzing-Aarts FV, van der Dijs FP, Muskiet FA, Duits AJ. The association of pre-eclampsia with the Duffy negative phenotype in women of West African descent. Br J Obstet Gynecol. 2002;109:453–5.Google Scholar
  23. 23.
    Velzing-Aarts FV, Muskiet FA, van der Dijs FP, Duits AJ. High serum interleukin-8 levels in afro-caribbean women with pre-eclampsia. Relations with tumor necrosis factor-alpha, duffy negative phenotype and von Willebrand factor. Am J Reprod Immunol. 2002;48:319–22.PubMedCrossRefGoogle Scholar
  24. 24.
    Woolley IJ, Wood EM, Sramkoski RM, Zimmerman PA, Miller JP, Kazura JW. Expression of Duffy antigen receptor for chemokines during reticulocyte maturation: using a CD71 flow cytometric technique to identify reticulocytes. Immunohematology. 2005;21:15–20.PubMedGoogle Scholar
  25. 25.
    Miller LH, Mason SJ, Clyde DF, McGinniss MH. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med. 1976;295:302–4.PubMedGoogle Scholar
  26. 26.
    Tournamille C, Colin Y, Cartron JP, Le Van Kim C. Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet. 1995;10:224–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Peiper SC, Wang ZX, Neote K, Martin AW, Showell HJ, Conklyn MJ, et al. The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. J Exp Med. 1995;181:1311–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Tournamille C, Le Van Kim C, Gane P, Cartron JP, Colin Y. Molecular basis and PCR-DNA typing of the Fya/fyb blood group polymorphism. Hum Genet. 1995;95:407–10.PubMedCrossRefGoogle Scholar
  29. 29.
    Michon P, Woolley I, Wood EM, Kastens W, Zimmerman PA, Adams JH. Duffy-null promoter heterozygosity reduces DARC expression and abrogates adhesion of the P. vivax ligand required for blood-stage infection. FEBS Lett. 2001;495:111–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Michon P, Fraser T, Adams JH. Naturally acquired and vaccine-elicited antibodies block erythrocyte cytoadherence of the Plasmodium vivax Duffy binding protein. Infect Immun. 2000;68:3164–71.PubMedCrossRefGoogle Scholar
  31. 31.
    Grimberg BT, Udomsangpetch R, Xainli J, McHenry A, Panichakul T, Sattabongkot J, et al. Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Med. 2007;4:e337.PubMedCrossRefGoogle Scholar
  32. 32.
    Beeson JG, Crabb BS. Towards a vaccine against Plasmodium vivax malaria. PLoS Med. 2007;4:e350.PubMedCrossRefGoogle Scholar
  33. 33.
    Xu L, Ashkenazi A, Chaudhuri A. Duffy antigen/receptor for chemokines (DARC) attenuates angiogenesis by causing senescence in endothelial cells. Angiogenesis. 2007;10:307–18.PubMedCrossRefGoogle Scholar
  34. 34.
    Bandyopadhyay S, Zhan R, Chaudhuri A, Watabe M, Pai SK, Hirota S, et al. Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nat Med. 2006;12:933–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Horton LW, Yu Y, Zaja-Milatovic S, Strieter RM, Richmond A. Opposing roles of murine Duffy antigen receptor for chemokine and murine CXC chemokine receptor-2 receptors in murine melanoma tumor growth. Cancer Res. 2007;67:9791–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Shen H, Schuster R, Stringer KF, Waltz SE, Lentsch AB. The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth. FASEB J. 2006;20:59–64.PubMedCrossRefGoogle Scholar
  37. 37.
    Addison CL, Belperio JA, Burdick MD, Strieter RM. Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis. BMC Cancer. 2004;4:28.PubMedCrossRefGoogle Scholar
  38. 38.
    Wang J, Ou ZL, Hou YF, Luo JM, Shen ZZ, Ding J, et al. Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Oncogene. 2006;25:7201–11.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  1. 1.Department of Infectious DiseasesMonash Medical CentreClaytonAustralia
  2. 2.Department of MedicineMonash UniversityClaytonAustralia

Personalised recommendations