The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CCL5  -  chemokine (C-C motif) ligand 5

Homo sapiens

Synonyms: C-C motif chemokine 5, D17S136E, EoCP, Eosinophil chemotactic cytokine, MGC17164, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CCL5


Psychiatry related information on CCL5


High impact information on CCL5

  • The identification of other members of this family, including receptors for the chemokines IL-8 and Mip-1/Rantes, thrombin, formyl peptide, and platelet activating factor, provide new tools for understanding structure-function relationships relevant to the inflammatory process [8].
  • Within 1 month of allo-immunization, there was significant upregulation in the concentrations of CD8 cell-derived suppressor factor activity, RANTES, and macrophage inflammatory proteins 1alpha and 1beta [9].
  • It also inhibits binding of the CXC-chemokine, SDF-1alpha, to CXCR4 and subsequent signal transduction, but does not itself cause signaling and has no effect on RANTES signaling via CCR5 [10].
  • This association appears to have a functional significance, because heparan sulphate facilitates RANTES inhibition of HIV-1 infection of monocytes [11].
  • Using granzyme A as a marker of cytolytic granule proteins, and macrophage inflammatory protein (MIP)-1alpha and RANTES as markers of HIV-1 inhibitory chemokines, we show that these two very different mediators of viral inhibition are both localized in the cytolytic granules of HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL) [11].

Chemical compound and disease context of CCL5

  • Steroid therapy altered serum levels of CCL2 and CCL5 chemokines in multiple sclerosis patients during relapse [12].
  • Conversely, infection of 3T3-CCR5 cells can be inhibited by RANTES, anti-CCR5 polyclonal antibody, or herbimycin A but not by monoclonal antibodies that block HIV-1 infection or by pertussis toxin [13].
  • Interestingly, exogenous heparan sulfate alone was able to substantially inhibit HIV-1 infection, an effect which was potentiated by RANTES or SDF-1 in the HIV-1-infection with R5 or X4 isolates [14].
  • In conclusion, chemokines monocyte chemotactive protein-1 and single cysteine motif-1alpha are, in addition to RANTES, associated with the development of alveolitis in sarcoidosis and their expression parallels the disease course [15].
  • After 1 h pretreatment, combined treatment significantly inhibited rhinovirus 16, 1B, and IL-1beta-induced CCL5 and CXCL8 protein and mRNA production in BEAS-2B cells compared with fluticasone alone [16].

Biological context of CCL5


Anatomical context of CCL5

  • In vitro and in vivo studies in human cell lines and primary T cells showed that synthetic peptides containing these residues blocked responses induced by the CCR5 ligand CCL5 [21].
  • In contrast, CCL5 enhanced the GTP binding to G(i alpha) and G(q alpha) in memory CD4(+) T cells, but not in naive CD4(+) T cells [17].
  • Conditioned medium from tuberculosis-infected human monocytes (CoMTB) stimulated significant CCL5 secretion from A549 cells and from primary alveolar, but not upper airway, epithelial cells [3].
  • Pretreatment of cell membrane fractions from memory and naive CD4(+) T cells with GTP-gamma S inhibited CCL5 binding, indicating the involvement of G proteins in the interaction of CCL5 and its receptor(s) [17].
  • Melanoma-inducible CCL5 (RANTES) production by infiltrating CD8 cells activates an apoptotic pathway in TIL involving cytochrome c release into the cytosol and activation of caspase-9 and -3 [4].

Associations of CCL5 with chemical compounds

  • The chemokine RANTES (regulated on activation normal T cell expressed and secreted; CCL5) binds selectively to glycosaminoglycans (GAGs) such as heparin, chondroitin sulfate, and dermatan sulfate [22].
  • Cytokine-stimulated endothelial cells also showed an increase in their potential to bind RANTES (CCL5); this was abrogated by chlorate blockade of sulphotransferase activity or by heparitinase cleavage of cell surface HS [23].
  • Sphingosine 1 phosphate (SPP), dihydro SPP (DHSPP) or the CC chemokine RANTES (CCL5), but not sphingosine induces the chemotaxis of these cells [24].
  • CCL5 was found to stimulate PCa cell invasion, and TAK-779 blocked the effects of CCL5 [25].
  • Treatment with the mu-opioid receptor agonist DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin), the chemokine RANTES (Regulated on Activation, Normal T cell-Expressed and -Secreted) (CCL5), or both, did not affect the level of coimmunoprecipitation [26].
  • The RANTES -28 C/G polymorphism was associated with the duration of clinical response to intraarticular triamcinolone injection, with patients carrying the RANTES -28G allele showing shorter duration of clinical response [27].

Physical interactions of CCL5

  • RANTES and other chemokines that interact with CCR5 and block infection of peripheral blood mononuclear cell cultures inhibit infection of primary macrophages inefficiently at best [28].
  • Efficient leukocyte arrest in flow but not transmigration may thus require the presentation of RANTES oligomers to bridge surface-bound RANTES and CCR1 [29].
  • Finally, RANTES forms GAG-dependent complexes with the shed ectodomains of SD-1 and SD-4 as well as with those of CD44 [30].
  • In vivo, anti-CCR5 antibody was able to almost completely inhibit the recruitment of monocytes/macrophages and T-helper (Th)1-type cells to inhibit partially the attraction of memory T cells, but had no effect on eosinophil infiltration, although all these cell types express other CCL5 binding chemokine receptors than CCR5 [19].
  • These results suggest that MCP-1 and RANTES receptors are promiscuously coupled to multiple G proteins in IANK cell membranes and that this coupling is different from MIP-1 alpha receptors, which seem to be coupled to G(s), G(o), and G(z) but not to G(i) [31].

Co-localisations of CCL5

  • Immunoreactivity for IL-4 and RANTES co-localized with MBP in maturing colony eosinophils on day 23 of culture in semisolid media, as judged by CLSM [32].

Regulatory relationships of CCL5

  • Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1alpha and MIP-1beta, but not by SDF-1 [33].
  • RANTES was expressed almost exclusively by T cells whereas the expression of MCP-1, MIP-1alpha, and MIP-1beta was confined largely to macrophages [34].
  • The molar concentration of LEC required to induce maximum cell migration is 20- to 200-fold greater than that required for RANTES or I309, respectively [35].
  • AOP-RANTES is found to inhibit CCR3-mediated HIV-1 infection with moderate potency, in contrast to its potent inhibition of CCR5-mediated HIV-1 infection [36].
  • CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed and secreted) inhibit CD4/CCR5-mediated HIV-1 cell fusion [37].

Other interactions of CCL5

  • Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES [33].
  • The C-C chemokines RANTES, MIP-1 alpha and MIP-1 beta were recently identified as the major components of the HIV-SF produced by both immortalized and primary patient CD8 T cells [38].
  • A derivative of RANTES that was created by chemical modification of the amino terminus, aminooxypentane (AOP)-RANTES, did not induce chemotaxis and was a subnanomolar antagonist of CCR5 function in monocytes [28].
  • This study shows that MCP-3 combines the properties of RANTES, a powerful chemoattractant, and MCP-1, a highly effective stimulus of mediator release, and thus has a particularly broad range of activities toward both human basophil and eosinophil leukocytes [39].
  • Although there is a mounting body of evidence that eosinophils are recruited to sites of allergic inflammation by a number of beta-chemokines, particularly eotaxin and RANTES, the receptor that mediates these actions has not been identified [40].

Analytical, diagnostic and therapeutic context of CCL5


  1. RANTES (CCL5) uses the proteoglycan CD44 as an auxiliary receptor to mediate cellular activation signals and HIV-1 enhancement. Roscic-Mrkic, B., Fischer, M., Leemann, C., Manrique, A., Gordon, C.J., Moore, J.P., Proudfoot, A.E., Trkola, A. Blood (2003) [Pubmed]
  2. Preferential targeting of CD4-CCR5 complexes with bifunctional inhibitors: a novel approach to block HIV-1 infection. Mack, M., Pfirstinger, J., Haas, J., Nelson, P.J., Kufer, P., Riethmüller, G., Schlöndorff, D. J. Immunol. (2005) [Pubmed]
  3. Transcriptional mechanisms regulating alveolar epithelial cell-specific CCL5 secretion in pulmonary tuberculosis. Wickremasinghe, M.I., Thomas, L.H., O'Kane, C.M., Uddin, J., Friedland, J.S. J. Biol. Chem. (2004) [Pubmed]
  4. A potential immune escape mechanism by melanoma cells through the activation of chemokine-induced T cell death. Mellado, M., de Ana, A.M., Moreno, M.C., Martínez, C., Rodríguez-Frade, J.M. Curr. Biol. (2001) [Pubmed]
  5. Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis. Glass, W.G., Hickey, M.J., Hardison, J.L., Liu, M.T., Manning, J.E., Lane, T.E. J. Immunol. (2004) [Pubmed]
  6. Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Kelder, W., McArthur, J.C., Nance-Sproson, T., McClernon, D., Griffin, D.E. Ann. Neurol. (1998) [Pubmed]
  7. CCR2-64I polymorphism and CCR5Delta32 deletion in patients with Alzheimer's disease. Galimberti, D., Fenoglio, C., Lovati, C., Gatti, A., Guidi, I., Venturelli, E., Cutter, G.R., Mariani, C., Forloni, G., Pettenati, C., Baron, P., Conti, G., Bresolin, N., Scarpini, E. J. Neurol. Sci. (2004) [Pubmed]
  8. C5A anaphylatoxin and its seven transmembrane-segment receptor. Gerard, C., Gerard, N.P. Annu. Rev. Immunol. (1994) [Pubmed]
  9. Allo-immunization elicits CD8+ T cell-derived chemokines, HIV suppressor factors and resistance to HIV infection in women. Wang, Y., Tao, L., Mitchell, E., Bravery, C., Berlingieri, P., Armstrong, P., Vaughan, R., Underwood, J., Lehner, T. Nat. Med. (1999) [Pubmed]
  10. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Donzella, G.A., Schols, D., Lin, S.W., Esté, J.A., Nagashima, K.A., Maddon, P.J., Allaway, G.P., Sakmar, T.P., Henson, G., De Clercq, E., Moore, J.P. Nat. Med. (1998) [Pubmed]
  11. Beta-chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans. Wagner, L., Yang, O.O., Garcia-Zepeda, E.A., Ge, Y., Kalams, S.A., Walker, B.D., Pasternack, M.S., Luster, A.D. Nature (1998) [Pubmed]
  12. Steroid therapy altered serum levels of CCL2 and CCL5 chemokines in multiple sclerosis patients during relapse. Bartosik-Psujek, H., Stelmasiak, Z. Eur. Neurol. (2004) [Pubmed]
  13. Use of chemokine receptors by poxviruses. Lalani, A.S., Masters, J., Zeng, W., Barrett, J., Pannu, R., Everett, H., Arendt, C.W., McFadden, G. Science (1999) [Pubmed]
  14. A new possible mechanism of human immunodeficiency virus type 1 infection of neural cells. Alvarez Losada, S., Cantó-Nogués, C., Muñoz-Fernández, M.A. Neurobiol. Dis. (2002) [Pubmed]
  15. CC and C chemokine expression in pulmonary sarcoidosis. Petrek, M., Kolek, V., Szotkowská, J., du Bois, R.M. Eur. Respir. J. (2002) [Pubmed]
  16. Combination therapy: synergistic suppression of virus-induced chemokines in airway epithelial cells. Edwards, M.R., Johnson, M.W., Johnston, S.L. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  17. An abortive ligand-induced activation of CCR1-mediated downstream signaling event and a deficiency of CCR5 expression are associated with the hyporesponsiveness of human naive CD4+ T cells to CCL3 and CCL5. Sato, K., Kawasaki, H., Morimoto, C., Yamashima, N., Matsuyama, T. J. Immunol. (2002) [Pubmed]
  18. CP-481,715, a potent and selective CCR1 antagonist with potential therapeutic implications for inflammatory diseases. Gladue, R.P., Tylaska, L.A., Brissette, W.H., Lira, P.D., Kath, J.C., Poss, C.S., Brown, M.F., Paradis, T.J., Conklyn, M.J., Ogborne, K.T., McGlynn, M.A., Lillie, B.M., DiRico, A.P., Mairs, E.N., McElroy, E.B., Martin, W.H., Stock, I.A., Shepard, R.M., Showell, H.J., Neote, K. J. Biol. Chem. (2003) [Pubmed]
  19. CCR5 usage by CCL5 induces a selective leukocyte recruitment in human skin xenografts in vivo. de Nadaï, P., Chenivesse, C., Gilet, J., Porte, H., Vorng, H., Chang, Y., Walls, A.F., Wallaert, B., Tonnel, A.B., Tsicopoulos, A., Zerwes, H.G. J. Invest. Dermatol. (2006) [Pubmed]
  20. Transactivation of the CCL5/RANTES gene by Epstein-Barr virus latent membrane protein 1. Uchihara, J.N., Krensky, A.M., Matsuda, T., Kawakami, H., Okudaira, T., Masuda, M., Ohta, T., Takasu, N., Mori, N. Int. J. Cancer (2005) [Pubmed]
  21. Identification of amino acid residues crucial for chemokine receptor dimerization. Hernanz-Falcón, P., Rodríguez-Frade, J.M., Serrano, A., Juan, D., del Sol, A., Soriano, S.F., Roncal, F., Gómez, L., Valencia, A., Martínez-A, C., Mellado, M. Nat. Immunol. (2004) [Pubmed]
  22. The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity. Proudfoot, A.E., Fritchley, S., Borlat, F., Shaw, J.P., Vilbois, F., Zwahlen, C., Trkola, A., Marchant, D., Clapham, P.R., Wells, T.N. J. Biol. Chem. (2001) [Pubmed]
  23. Endothelial inflammation: the role of differential expression of N-deacetylase/N-sulphotransferase enzymes in alteration of the immunological properties of heparan sulphate. Carter, N.M., Ali, S., Kirby, J.A. J. Cell. Sci. (2003) [Pubmed]
  24. Sphingosine 1 phosphate induces the chemotaxis of human natural killer cells. Role for heterotrimeric G proteins and phosphoinositide 3 kinases. Kveberg, L., Bryceson, Y., Inngjerdingen, M., Rolstad, B., Maghazachi, A.A. Eur. J. Immunol. (2002) [Pubmed]
  25. Expression of CCL5 (RANTES) and CCR5 in prostate cancer. Vaday, G.G., Peehl, D.M., Kadam, P.A., Lawrence, D.M. Prostate (2006) [Pubmed]
  26. Heterodimerization and cross-desensitization between the mu-opioid receptor and the chemokine CCR5 receptor. Chen, C., Li, J., Bot, G., Szabo, I., Rogers, T.J., Liu-Chen, L.Y. Eur. J. Pharmacol. (2004) [Pubmed]
  27. Association of RANTES promoter polymorphism with juvenile rheumatoid arthritis. Yao, T.C., Tsai, Y.C., Huang, J.L. Arthritis Rheum. (2009) [Pubmed]
  28. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Simmons, G., Clapham, P.R., Picard, L., Offord, R.E., Rosenkilde, M.M., Schwartz, T.W., Buser, R., Wells, T.N., Proudfoot, A.E. Science (1997) [Pubmed]
  29. Oligomerization of RANTES is required for CCR1-mediated arrest but not CCR5-mediated transmigration of leukocytes on inflamed endothelium. Baltus, T., Weber, K.S., Johnson, Z., Proudfoot, A.E., Weber, C. Blood (2003) [Pubmed]
  30. RANTES (CCL5) induces a CCR5-dependent accelerated shedding of syndecan-1 (CD138) and syndecan-4 from HeLa cells and forms complexes with the shed ectodomains of these proteoglycans as well as with those of CD44. Charnaux, N., Brule, S., Chaigneau, T., Saffar, L., Sutton, A., Hamon, M., Prost, C., Lievre, N., Vita, C., Gattegno, L. Glycobiology (2005) [Pubmed]
  31. Differential coupling of CC chemokine receptors to multiple heterotrimeric G proteins in human interleukin-2-activated natural killer cells. al-Aoukaty, A., Schall, T.J., Maghazachi, A.A. Blood (1996) [Pubmed]
  32. Interleukin-4 and RANTES expression in maturing eosinophils derived from human cord blood CD34+ progenitors. Velazquez, J.R., Lacy, P., Mahmudi-Azer, S., Bablitz, B., Milne, C.D., Denburg, J.A., Moqbel, R. Immunology (2000) [Pubmed]
  33. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Scarlatti, G., Tresoldi, E., Björndal, A., Fredriksson, R., Colognesi, C., Deng, H.K., Malnati, M.S., Plebani, A., Siccardi, A.G., Littman, D.R., Fenyö, E.M., Lusso, P. Nat. Med. (1997) [Pubmed]
  34. CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease. Buri, C., Körner, M., Schärli, P., Cefai, D., Uguccioni, M., Mueller, C., Laissue, J.A., Mazzucchelli, L. Blood (2001) [Pubmed]
  35. LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8. Howard, O.M., Dong, H.F., Shirakawa, A.K., Oppenheim, J.J. Blood (2000) [Pubmed]
  36. Differential activation of CC chemokine receptors by AOP-RANTES. Elsner, J., Mack, M., Brühl, H., Dulkys, Y., Kimmig, D., Simmons, G., Clapham, P.R., Schlöndorff, D., Kapp, A., Wells, T.N., Proudfoot, A.E. J. Biol. Chem. (2000) [Pubmed]
  37. Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication. Gong, W., Howard, O.M., Turpin, J.A., Grimm, M.C., Ueda, H., Gray, P.W., Raport, C.J., Oppenheim, J.J., Wang, J.M. J. Biol. Chem. (1998) [Pubmed]
  38. The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Cocchi, F., DeVico, A.L., Garzino-Demo, A., Cara, A., Gallo, R.C., Lusso, P. Nat. Med. (1996) [Pubmed]
  39. Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine. Dahinden, C.A., Geiser, T., Brunner, T., von Tscharner, V., Caput, D., Ferrara, P., Minty, A., Baggiolini, M. J. Exp. Med. (1994) [Pubmed]
  40. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. Daugherty, B.L., Siciliano, S.J., DeMartino, J.A., Malkowitz, L., Sirotina, A., Springer, M.S. J. Exp. Med. (1996) [Pubmed]
  41. Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue. Fischer, M., Juremalm, M., Olsson, N., Backlin, C., Sundström, C., Nilsson, K., Enblad, G., Nilsson, G. Int. J. Cancer (2003) [Pubmed]
  42. Gene expression profile activated by the chemokine CCL5/RANTES in human neuronal cells. Valerio, A., Ferrario, M., Martinez, F.O., Locati, M., Ghisi, V., Bresciani, L.G., Mantovani, A., Spano, P. J. Neurosci. Res. (2004) [Pubmed]
  43. Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. Brühl, H., Vielhauer, V., Weiss, M., Mack, M., Schlöndorff, D., Segerer, S. Rheumatology (Oxford, England) (2005) [Pubmed]
WikiGenes - Universities