Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Carlos Eduardo Repeke
  • Thiago Pompermaier Garlet
  • Andreia Espíndola Vieira
  • Daiana Broll
  • Fernando Queiroz Cunha
  • Gustavo Pompermaier GarletEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_580



Historical Background

CCL5 was initially described in 1988 and this new protein was named for its characteristics: Regulated upon Activation expressed by Normal T cells and presumably Secreted (RANTES) (Schall et al. 1988). A relatively new technology, at the time, was used to identify RANTES, subtraction cDNA libraries, which help to distinguish genes expressed in one cell and not in another. This genetic approach has since led to the uncovering of about 50 other chemokines, and in order to clarify the nomenclature of all chemokines and their receptors, a new nomenclature has been introduced, in which RANTES has been renamed CCL5 (Zlotnik and Yoshie 2000). CCL5 was first discovered in T cell-specific cDNA, and this initial report on CCL5 placed further attention on a new family of chemotactic proteins that proved to be important in influencing a series of biologic and pathological processes (Levy 2009).

Collectively, chemokines are defined as small (8–14 kDa) proteins...

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


  1. Appay V, Rowland-Jones SL. RANTES: a versatile and controversial chemokine. Trends Immunol. 2001;22(2):83–7.PubMedCrossRefGoogle Scholar
  2. Barrios CS, Castillo L, Giam C, Wu L, Beilke MA. Inhibition of HIV type 1 replication by human T lymphotropic virus types 1 and 2 tax proteins in vitro. AIDS Res Hum Retrovir. 2013;29(7):1061–7.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bianchi R, Kastrisianaki E, Giambanco I, Donato R. S100B protein stimulates microglia migration via RAGE-dependent up-regulation of chemokine expression and release. J Biol Chem. 2011;286(9):7214–26.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Carrington M, Dean M, Martin MP, O’Brien SJ. Genetics of HIV-1 infection: chemokine receptor CCR5 polymorphism and its consequences. Hum Mol Genet. 1999;8(10):1939–45.PubMedCrossRefGoogle Scholar
  5. Cheng JF, Jack R. CCR1 antagonists. Mol Divers. 2008;12(1):17–23.PubMedCrossRefGoogle Scholar
  6. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995;270(5243):1811–5.PubMedCrossRefGoogle Scholar
  7. Conti P, DiGioacchino M. MCP-1 and RANTES are mediators of acute and chronic inflammation. Allergy Asthma Proc. 2001;22(3):133–7.PubMedCrossRefGoogle Scholar
  8. Doodes PD, Cao Y, Hamel KM, Wang Y, Rodeghero RL, Kobezda T, et al. CCR5 is involved in resolution of inflammation in proteoglycan-induced arthritis. Arthritis Rheum. 2009;60(10):2945–53.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Graziano FM, Cook EB, Stahl JL. Cytokines, chemokines, RANTES, and eotaxin. Allergy Asthma Proc. 1999;20(3):141–6.PubMedCrossRefGoogle Scholar
  10. Horuk R. Chemokine receptors. Cytokine Growth Factor Rev. 2001;12(4):313–35.PubMedCrossRefGoogle Scholar
  11. Ishida T, Ueda R. CCR4 as a novel molecular target for immunotherapy of cancer. Cancer Sci. 2006;97(11):1139–46.PubMedCrossRefGoogle Scholar
  12. Levy JA. The unexpected pleiotropic activities of RANTES. J Immunol. 2009;182(7):3945–6.PubMedCrossRefGoogle Scholar
  13. Maurer M, von Stebut E. Macrophage inflammatory protein-1. Int J Biochem Cell Biol. 2004;36(10):1882–6.PubMedCrossRefGoogle Scholar
  14. Menten P, Wuyts A, Van Damme J. Macrophage inflammatory protein-1. Cytokine Growth Factor Rev. 2002;13(6):455–81.PubMedCrossRefGoogle Scholar
  15. Neote K, DiGregorio D, Mak JY, Horuk R, Schall TJ. Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor. Cell. 1993;72(3):415–25.PubMedCrossRefGoogle Scholar
  16. Power CA, Meyer A, Nemeth K, Bacon KB, Hoogewerf AJ, Proudfoot AE, et al. Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line. J Biol Chem. 1995;270(33):19495–500.PubMedCrossRefGoogle Scholar
  17. Proudfoot AE, Power CA, Hoogewerf AJ, Montjovent MO, Borlat F, Offord RE, et al. Extension of recombinant human RANTES by the retention of the initiating methionine produces a potent antagonist. J Biol Chem. 1996;271(5):2599–603.PubMedCrossRefGoogle Scholar
  18. Ramírez-Martínez G, Cruz-Lagunas A, Jiménez-Alvarez L, Espinosa E, Ortíz-Quintero B, Santos-Mendoza T, et al. Seasonal and pandemic influenza H1N1 viruses induce differential expression of SOCS-1 and RIG-I genes and cytokine/chemokine production in macrophages. Cytokines. 2013;62(1):151–9.CrossRefGoogle Scholar
  19. Repeke CE, Ferreira Jr SB, Claudino M, Silveira EM, de Assis GF, Avila-Campos MJ, et al. Evidences of the cooperative role of the chemokines CCL3, CCL4 and CCL5 and its receptors CCR1+ and CCR5+ in RANKL+ cell migration throughout experimental periodontitis in mice. Bone. 2010;46(4):1122–30.PubMedCrossRefGoogle Scholar
  20. Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996;35(11):3362–7.PubMedCrossRefGoogle Scholar
  21. Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, et al. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988;141(3):1018–25.PubMedPubMedCentralGoogle Scholar
  22. Wells TN, Proudfoot AE, Power CA. Chemokine receptors and their role in leukocyte activation. Immunol Lett. 1999;65(1–2):35–40.PubMedCrossRefGoogle Scholar
  23. Zhang Q, Qin J, Zhong L, Gong L, Zhang B, Zhang Y, et al. CCL5-mediated Th2 immune polarization promotes metastasis in luminal breast cancer. Cancer Res. 2015;75(20):4312–21.PubMedCrossRefGoogle Scholar
  24. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000;12(2):121–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Carlos Eduardo Repeke
    • 1
  • Thiago Pompermaier Garlet
    • 2
  • Andreia Espíndola Vieira
    • 3
  • Daiana Broll
    • 4
  • Fernando Queiroz Cunha
    • 5
  • Gustavo Pompermaier Garlet
    • 3
    Email author
  1. 1.PPGCAS Lab, Department of Dentistry of LagartoFederal University of Sergipe – DOL/UFSLagartoBrazil
  2. 2.Department of Structural and Molecular Biology and GeneticsState University of Ponta GrossaPonta GrossaBrazil
  3. 3.OSTEOimmunology Lab, Department of Biological Sciences, School of Dentistry of BauruSão Paulo University, FOB/USPBauruBrazil
  4. 4.PPGCSFederal Unversity of SergipeSão CristóvãoBrazil
  5. 5.Inflammation lab, Department of Pharmacology, School of Medicine of Ribeirão PretoSão Paulo University – FMRP/USPBauruBrazil