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Gene Review

CCL8  -  chemokine (C-C motif) ligand 8

Homo sapiens

Synonyms: C-C motif chemokine 8, HC14, MCP-2, MCP2, Monocyte chemoattractant protein 2, ...
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Disease relevance of CCL8


High impact information on CCL8

  • Dendritic cells in the lymph nodes of macaques infected with simian immunodeficiency virus (SIV) have elevated levels of monocyte chemoattractant protein 2 (MCP-2), demonstrating that chemokine induction also occurs during retroviral infection in vivo [6].
  • These results demonstrate that MCP-1, MCP-2, and MCP-3 are inflammatory mediators that specifically stimulate the directional migration of T cells as well as monocytes and may play an important role in immune cell recruitment into sites of antigenic challenge [7].
  • Of note, the addition of optimal concentrations of recombinant CCL8 plus CXCL10 to endothelial cultures completely restored the proadhesive activity of TNF-alpha [8].
  • TRAIL counteracts the proadhesive activity of inflammatory cytokines in endothelial cells by down-modulating CCL8 and CXCL10 chemokine expression and release [8].
  • A29S displayed an unusual pharmacological profile, binding and responding to MCP-2 similarly to wtCCR5, but exhibiting severely impaired binding and functional responses to MIP-1alpha, MIP-1beta, and RANTES [9].

Chemical compound and disease context of CCL8


Biological context of CCL8


Anatomical context of CCL8


Associations of CCL8 with chemical compounds


Physical interactions of CCL8

  • Desensitization studies indicate that MCP-2 interacts with receptors recognizing MCP-1 as well as RANTES [15].
  • MCP-2 is a potent inhibitor of HIV-1 by virtue of its high-affinity binding to the receptor CCR5, one of the major coreceptors for HIV-1 [20].

Regulatory relationships of CCL8

  • At 4 nM, MCP-2 induced a Ca2+ influx which was as potent as that with MCP-1 at 4 nM, although the increase by MCP-2 became saturated at higher concentrations [21].
  • Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication [2].
  • We demonstrate that MCP-2 specifically inhibits replication of R5 HIV-1 and that this activity is additive to that of RANTES [5].

Other interactions of CCL8

  • We conclude that MCP-3, but not MCP-2, is a functional ligand for the MCP-1 receptor [13].
  • In this study, we have examined potential interactions of MCP-2 and MCP-3 with the recently cloned MCP-1 receptor [13].
  • Both CCR1- and CCR2B-transfected 293 cells showed significant migration in response to MCP-2, in addition to responding to other specific chemokines [11].
  • In conclusion, our study suggests a possible role of the polymorphisms CCR5-delta32, RANTES -403, and MCP-2 Q46K in the outcome of HCV infection [1].
  • Monocyte chemoattractant protein-2 is a potent agonist of CCR2B [22].

Analytical, diagnostic and therapeutic context of CCL8


  1. Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hellier, S., Frodsham, A.J., Hennig, B.J., Klenerman, P., Knapp, S., Ramaley, P., Satsangi, J., Wright, M., Zhang, L., Thomas, H.C., Thursz, M., Hill, A.V. Hepatology (2003) [Pubmed]
  2. 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]
  3. Functional comparison of two human monocyte chemotactic protein-2 isoforms, role of the amino-terminal pyroglutamic acid and processing by CD26/dipeptidyl peptidase IV. Van Coillie, E., Proost, P., Van Aelst, I., Struyf, S., Polfliet, M., De Meester, I., Harvey, D.J., Van Damme, J., Opdenakker, G. Biochemistry (1998) [Pubmed]
  4. Patterns of protein expression in infectious meningitis: a cerebrospinal fluid protein array analysis. Kastenbauer, S., Angele, B., Sporer, B., Pfister, H.W., Koedel, U. J. Neuroimmunol. (2005) [Pubmed]
  5. Monocyte chemoattractant protein-2 (CC chemokine ligand 8) inhibits replication of human immunodeficiency virus type 1 via CC chemokine receptor 5. Yang, O.O., Garcia-Zepeda, E.A., Walker, B.D., Luster, A.D. J. Infect. Dis. (2002) [Pubmed]
  6. HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Izmailova, E., Bertley, F.M., Huang, Q., Makori, N., Miller, C.J., Young, R.A., Aldovini, A. Nat. Med. (2003) [Pubmed]
  7. Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes. Taub, D.D., Proost, P., Murphy, W.J., Anver, M., Longo, D.L., van Damme, J., Oppenheim, J.J. J. Clin. Invest. (1995) [Pubmed]
  8. TRAIL counteracts the proadhesive activity of inflammatory cytokines in endothelial cells by down-modulating CCL8 and CXCL10 chemokine expression and release. Secchiero, P., Corallini, F., di Iasio, M.G., Gonelli, A., Barbarotto, E., Zauli, G. Blood (2005) [Pubmed]
  9. Multiple nonfunctional alleles of CCR5 are frequent in various human populations. Blanpain, C., Lee, B., Tackoen, M., Puffer, B., Boom, A., Libert, F., Sharron, M., Wittamer, V., Vassart, G., Doms, R.W., Parmentier, M. Blood (2000) [Pubmed]
  10. Plasma levels of the chemokines monocyte chemotactic proteins-1 and -2 are elevated in human sepsis. Bossink, A.W., Paemen, L., Jansen, P.M., Hack, C.E., Thijs, L.G., Van Damme, J. Blood (1995) [Pubmed]
  11. Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors. Gong, X., Gong, W., Kuhns, D.B., Ben-Baruch, A., Howard, O.M., Wang, J.M. J. Biol. Chem. (1997) [Pubmed]
  12. The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2. Van Coillie, E., Fiten, P., Nomiyama, H., Sakaki, Y., Miura, R., Yoshie, O., Van Damme, J., Opdenakker, G. Genomics (1997) [Pubmed]
  13. Monocyte chemoattractant protein-3, but not monocyte chemoattractant protein-2, is a functional ligand of the human monocyte chemoattractant protein-1 receptor. Franci, C., Wong, L.M., Van Damme, J., Proost, P., Charo, I.F. J. Immunol. (1995) [Pubmed]
  14. Monocyte chemotactic protein-2, monocyte chemotactic protein-3, and fibroblast-induced cytokine. Three new chemokines induce chemotaxis and activation of basophils. Alam, R., Forsythe, P., Stafford, S., Heinrich, J., Bravo, R., Proost, P., Van Damme, J. J. Immunol. (1994) [Pubmed]
  15. Monocyte chemotactic protein MCP-2 activates human basophil and eosinophil leukocytes similar to MCP-3. Weber, M., Uguccioni, M., Ochensberger, B., Baggiolini, M., Clark-Lewis, I., Dahinden, C.A. J. Immunol. (1995) [Pubmed]
  16. Chemokine-mediated inflammation: Identification of a possible regulatory role for CCR2. O'boyle, G., Brain, J.G., Kirby, J.A., Ali, S. Mol. Immunol. (2007) [Pubmed]
  17. Receptors and transduction pathways for monocyte chemotactic protein-2 and monocyte chemotactic protein-3. Similarities and differences with MCP-1. Sozzani, S., Zhou, D., Locati, M., Rieppi, M., Proost, P., Magazin, M., Vita, N., van Damme, J., Mantovani, A. J. Immunol. (1994) [Pubmed]
  18. Human monocyte chemotactic protein-2: cDNA cloning and regulated expression of mRNA in mesenchymal cells. Van Coillie, E., Froyen, G., Nomiyama, H., Miura, R., Fiten, P., Van Aelst, I., Van Damme, J., Opdenakker, G. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  19. Regulation of the human chemokine receptor CCR1. Cross-regulation by CXCR1 and CXCR2. Richardson, R.M., Pridgen, B.C., Haribabu, B., Snyderman, R. J. Biol. Chem. (2000) [Pubmed]
  20. Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors. Blaszczyk, J., Coillie, E.V., Proost, P., Damme, J.V., Opdenakker, G., Bujacz, G.D., Wang, J.M., Ji, X. Biochemistry (2000) [Pubmed]
  21. Monocyte chemoattractant protein-2 can exert its effects through the MCP-1 receptor (CC CKR2B). Yamagami, S., Tanaka, H., Endo, N. FEBS Lett. (1997) [Pubmed]
  22. Monocyte chemoattractant protein-2 is a potent agonist of CCR2B. Moore, U.M., Kaplow, J.M., Pleass, R.D., Castro, S.W., Naik, K., Lynch, C.N., Daly, S., Roach, A.G., Jaye, M., Williams, R.J. J. Leukoc. Biol. (1997) [Pubmed]
  23. Induction of monocyte chemotactic proteins MCP-1 and MCP-2 in human fibroblasts and leukocytes by cytokines and cytokine inducers. Chemical synthesis of MCP-2 and development of a specific RIA. Van Damme, J., Proost, P., Put, W., Arens, S., Lenaerts, J.P., Conings, R., Opdenakker, G., Heremans, H., Billiau, A. J. Immunol. (1994) [Pubmed]
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