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Gene Review

CCR3  -  chemokine (C-C motif) receptor 3

Homo sapiens

Synonyms: C-C CKR-3, C-C chemokine receptor type 3, CC-CKR-3, CCR-3, CD193, ...
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Disease relevance of CCR3

  • Our results suggest that both CCR3 and CCR5 promote efficient infection of the CNS by HIV-1 [1].
  • Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma [2].
  • These findings suggest that multiple C-C chemokines, acting at least in part via CCR3, contribute to bronchial eosinophilia in both atopic and nonatopic asthma [3].
  • Suppression of IL-8/CXCL8 was abrogated in the presence of anti-CCR3 mAb, pertussis toxin, and wortmannin, indicating it was mediated by the CCR3 receptor, G(i) proteins, and phosphatidylinositol 3-kinase signaling [4].
  • We postulate that expression of CCR3 may underlie situations where both DCs and eosinophils accumulate in vivo, such as the lesions of patients with Langerhans cell granulomatosis [5].

Psychiatry related information on CCR3

  • Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains [6].

High impact information on CCR3

  • The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates [7].
  • CCR3 facilitated infection by a more restricted subset of primary viruses, and binding of the CCR3 ligand, eotaxin, inhibited infection by these isolates [7].
  • CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia [1].
  • By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage [8].
  • Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates [8].

Chemical compound and disease context of CCR3


Biological context of CCR3

  • Pretreatment of eosinophils with this mAb blocked chemotaxis and calcium flux induced by all CCR3 ligands [13].
  • The Th2-associated chemoattractant receptors CRTh2 and CCR3 were up-regulated with slower kinetics compared to the Th1-associated receptors CXCR3 and CXCR6, consistent with a different kinetics and efficiency of polarization [14].
  • Heparin inhibited intracellular calcium flux, respiratory burst and chemotactic responses of eosinophils to CCL11, but not to the chemoattractant C5a, and inhibited binding of CCL11 to CCR3 [15].
  • In receptor-binding assays, MIP-5 shows IC50 values of 12 nM for competition with 125I-MIP-1alpha for binding to CC-chemokine receptor (CCR)1, and 2.5 nM for competition with 125I-MCP-3 for binding to CCR3 [16].
  • The airway epithelium CCR3 receptor/eotaxin ligand signal transduction system may be an important target for development of novel mechanism-based adjunctive therapies designed to interrupt the underlying chronic inflammation in allergic and inflammatory disorders [17].

Anatomical context of CCR3


Associations of CCR3 with chemical compounds

  • The surface expression of CCR3 is not modulated following uptake of particulate substances such as zymosan or latex beads [5].
  • This demonstrates the importance of the penultimate proline in LD78beta(1 - 70) for CCR3 recognition [21].
  • Following treatment with the sulfation inhibitor chlorate or proteoglycanases, no inhibition of CCL11-induced activity was observed using either eosinophils or a CCR3-expressing transfectant cell line [15].
  • RESULTS: High percentages (>70%) of tryptase-positive cells showing CCR3 expression were found in the skin and in the intestinal submucosa, whereas much lower percentages (< or = 20%) were found in the intestinal mucosa and in the lung interstitium [22].
  • Antibody against eotaxin or CCR3, and actinomycin D inhibited these effects of eotaxin [23].

Physical interactions of CCR3

  • Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils [24].
  • In particular, modest variations in the pH and the level of sodium chloride over a range of physiologic and near physiologic conditions had dramatic effects on eotaxin binding and CCR3-mediated cytoplasmic Ca2+ mobilization [25].
  • Ecalectin did not mediate ECA activity by binding to the IL-5R or to CCR3 [26].
  • Surface epitopes identified on RANTES to be involved in binding to CCR3 are mimicked on the eotaxin-1 and MCP-3 surface [27].
  • A linear peptide corresponding to the N-terminal region of CCR3 binds to eotaxin-2, inducing concentration-dependent chemical shift changes or line broadening of many residues [28].

Regulatory relationships of CCR3


Other interactions of CCR3

  • CTL activity was abrogated by an antibody that blocks CCR3, further indicating that specific lysis is triggered via this chemokine receptor [18].
  • These observations reveal a novel mechanism for the induction of HIV-1-specific cytotoxicity that depends on RANTES acting via CCR3 [18].
  • In contrast, CCR3 and CCR4 were found on Th2s [33].
  • Direct receptor binding experiments with the CysL24-51 peptide confirmed binding to cells transfected with CCR2 and CCR3 [34].
  • Constitutive expression of CCR1 and CCR3 mRNA in PMN was detected by ribonuclease protection assay [35].

Analytical, diagnostic and therapeutic context of CCR3


  1. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. He, J., Chen, Y., Farzan, M., Choe, H., Ohagen, A., Gartner, S., Busciglio, J., Yang, X., Hofmann, W., Newman, W., Mackay, C.R., Sodroski, J., Gabuzda, D. Nature (1997) [Pubmed]
  2. Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma. Kleinhans, M., Tun-Kyi, A., Gilliet, M., Kadin, M.E., Dummer, R., Burg, G., Nestle, F.O. Blood (2003) [Pubmed]
  3. Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. Ying, S., Meng, Q., Zeibecoglou, K., Robinson, D.S., Macfarlane, A., Humbert, M., Kay, A.B. J. Immunol. (1999) [Pubmed]
  4. Eotaxin/CCL11 suppresses IL-8/CXCL8 secretion from human dermal microvascular endothelial cells. Cheng, S.S., Lukacs, N.W., Kunkel, S.L. J. Immunol. (2002) [Pubmed]
  5. Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by human dendritic cells. Beaulieu, S., Robbiani, D.F., Du, X., Rodrigues, E., Ignatius, R., Wei, Y., Ponath, P., Young, J.W., Pope, M., Steinman, R.M., Mojsov, S. J. Immunol. (2002) [Pubmed]
  6. Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their ligands in normal and Alzheimer's disease brains. Xia, M.Q., Qin, S.X., Wu, L.J., Mackay, C.R., Hyman, B.T. Am. J. Pathol. (1998) [Pubmed]
  7. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Choe, H., Farzan, M., Sun, Y., Sullivan, N., Rollins, B., Ponath, P.D., Wu, L., Mackay, C.R., LaRosa, G., Newman, W., Gerard, N., Gerard, C., Sodroski, J. Cell (1996) [Pubmed]
  8. 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]
  9. Characterization of chemokine CCR3 agonist-mediated eosinophil recruitment in the Brown-Norway rat. Kudlacz, E.M., Whitney, C.A., Andresen, C.J., Umland, J.P., Cheng, J.B. Br. J. Pharmacol. (1999) [Pubmed]
  10. A small molecule antagonist of chemokine receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. Sabroe, I., Peck, M.J., Van Keulen, B.J., Jorritsma, A., Simmons, G., Clapham, P.R., Williams, T.J., Pease, J.E. J. Biol. Chem. (2000) [Pubmed]
  11. The role of mitogen-activated protein kinases in eotaxin-induced cytokine production from bronchial epithelial cells. Cui, C.H., Adachi, T., Oyamada, H., Kamada, Y., Kuwasaki, T., Yamada, Y., Saito, N., Kayaba, H., Chihara, J. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  12. Allergen-induced fluctuation in CC chemokine receptor 3 expression on bone marrow CD34+ cells from asthmatic subjects: significance for mobilization of haemopoietic progenitor cells in allergic inflammation. Sehmi, R., Dorman, S., Baatjes, A., Watson, R., Foley, R., Ying, S., Robinson, D.S., Kay, A.B., O'Byrne, P.M., Denburg, J.A. Immunology (2003) [Pubmed]
  13. Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. Heath, H., Qin, S., Rao, P., Wu, L., LaRosa, G., Kassam, N., Ponath, P.D., Mackay, C.R. J. Clin. Invest. (1997) [Pubmed]
  14. Kinetics and expression patterns of chemokine receptors in human CD4+ T lymphocytes primed by myeloid or plasmacytoid dendritic cells. Langenkamp, A., Nagata, K., Murphy, K., Wu, L., Lanzavecchia, A., Sallusto, F. Eur. J. Immunol. (2003) [Pubmed]
  15. Proteoglycans are potent modulators of the biological responses of eosinophils to chemokines. Culley, F.J., Fadlon, E.J., Kirchem, A., Williams, T.J., Jose, P.J., Pease, J.E. Eur. J. Immunol. (2003) [Pubmed]
  16. Characterisation of macrophage inflammatory protein-5/human CC cytokine-2, a member of the macrophage-inflammatory-protein family of chemokines. Coulin, F., Power, C.A., Alouani, S., Peitsch, M.C., Schroeder, J.M., Moshizuki, M., Clark-Lewis, I., Wells, T.N. Eur. J. Biochem. (1997) [Pubmed]
  17. Cytokine-stimulated human lung alveolar epithelial cells release eotaxin-2 (CCL24) and eotaxin-3 (CCL26). Heiman, A.S., Abonyo, B.O., Darling-Reed, S.F., Alexander, M.S. J. Interferon Cytokine Res. (2005) [Pubmed]
  18. HIV-specific T cell cytotoxicity mediated by RANTES via the chemokine receptor CCR3. Hadida, F., Vieillard, V., Autran, B., Clark-Lewis, I., Baggiolini, M., Debré, P. J. Exp. Med. (1998) [Pubmed]
  19. High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines. Uguccioni, M., Mackay, C.R., Ochensberger, B., Loetscher, P., Rhis, S., LaRosa, G.J., Rao, P., Ponath, P.D., Baggiolini, M., Dahinden, C.A. J. Clin. Invest. (1997) [Pubmed]
  20. Recombinant IFN-alpha (2b) increases the expression of apoptosis receptor CD95 and chemokine receptors CCR1 and CCR3 in monocytoid cells. Zella, D., Barabitskaja, O., Casareto, L., Romerio, F., Secchiero, P., Reitz, M.S., Gallo, R.C., Weichold, F.F. J. Immunol. (1999) [Pubmed]
  21. Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils. Struyf, S., Menten, P., Lenaerts, J.P., Put, W., D'Haese, A., De Clercq, E., Schols, D., Proost, P., Van Damme, J. Eur. J. Immunol. (2001) [Pubmed]
  22. Expression of the chemokine receptor CCR3 on human mast cells. de Paulis, A., Annunziato, F., Di Gioia, L., Romagnani, S., Carfora, M., Beltrame, C., Marone, G., Romagnani, P. Int. Arch. Allergy Immunol. (2001) [Pubmed]
  23. Autocrine regulation of eotaxin in normal human bronchial epithelial cells. Saito, H., Shimizu, H., Akiyama, K. Int. Arch. Allergy Immunol. (2000) [Pubmed]
  24. Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils. White, J.R., Imburgia, C., Dul, E., Appelbaum, E., O'Donnell, K., O'Shannessy, D.J., Brawner, M., Fornwald, J., Adamou, J., Elshourbagy, N.A., Kaiser, K., Foley, J.J., Schmidt, D.B., Johanson, K., Macphee, C., Moores, K., McNulty, D., Scott, G.F., Schleimer, R.P., Sarau, H.M. J. Leukoc. Biol. (1997) [Pubmed]
  25. Chemokine receptor CCR3 function is highly dependent on local pH and ionic strength. Dairaghi, D.J., Oldham, E.R., Bacon, K.B., Schall, T.J. J. Biol. Chem. (1997) [Pubmed]
  26. Biological activities of ecalectin: a novel eosinophil-activating factor. Matsumoto, R., Hirashima, M., Kita, H., Gleich, G.J. J. Immunol. (2002) [Pubmed]
  27. Comparison of the structure of vMIP-II with eotaxin-1, RANTES, and MCP-3 suggests a unique mechanism for CCR3 activation. Fernandez, E.J., Wilken, J., Thompson, D.A., Peiper, S.C., Lolis, E. Biochemistry (2000) [Pubmed]
  28. NMR solution structure and receptor peptide binding of the CC chemokine eotaxin-2. Mayer, K.L., Stone, M.J. Biochemistry (2000) [Pubmed]
  29. The ligands of CXC chemokine receptor 3, I-TAC, Mig, and IP10, are natural antagonists for CCR3. Loetscher, P., Pellegrino, A., Gong, J.H., Mattioli, I., Loetscher, M., Bardi, G., Baggiolini, M., Clark-Lewis, I. J. Biol. Chem. (2001) [Pubmed]
  30. Chemokine receptors and virus entry in the central nervous system. Gabuzda, D., Wang, J. J. Neurovirol. (1999) [Pubmed]
  31. Chemokines and their receptors in the pathogenesis of allergic asthma: progress and perspective. Bisset, L.R., Schmid-Grendelmeier, P. Current opinion in pulmonary medicine. (2005) [Pubmed]
  32. Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells. Ying, S., Robinson, D.S., Meng, Q., Rottman, J., Kennedy, R., Ringler, D.J., Mackay, C.R., Daugherty, B.L., Springer, M.S., Durham, S.R., Williams, T.J., Kay, A.B. Eur. J. Immunol. (1997) [Pubmed]
  33. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. Sallusto, F., Lenig, D., Mackay, C.R., Lanzavecchia, A. J. Exp. Med. (1998) [Pubmed]
  34. HIV-1 Tat protein mimicry of chemokines. Albini, A., Ferrini, S., Benelli, R., Sforzini, S., Giunciuglio, D., Aluigi, M.G., Proudfoot, A.E., Alouani, S., Wells, T.N., Mariani, G., Rabin, R.L., Farber, J.M., Noonan, D.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  35. Granulocyte-macrophage colony stimulating factor up-regulates CCR1 in human neutrophils. Cheng, S.S., Lai, J.J., Lukacs, N.W., Kunkel, S.L. J. Immunol. (2001) [Pubmed]
  36. Eotaxin (CCL11) and eotaxin-2 (CCL24) induce recruitment of eosinophils, basophils, neutrophils, and macrophages as well as features of early- and late-phase allergic reactions following cutaneous injection in human atopic and nonatopic volunteers. Menzies-Gow, A., Ying, S., Sabroe, I., Stubbs, V.L., Soler, D., Williams, T.J., Kay, A.B. J. Immunol. (2002) [Pubmed]
  37. Macrophage-derived chemokine induces human eosinophil chemotaxis in a CC chemokine receptor 3- and CC chemokine receptor 4-independent manner. Bochner, B.S., Bickel, C.A., Taylor, M.L., MacGlashan, D.W., Gray, P.W., Raport, C.J., Godiska, R. J. Allergy Clin. Immunol. (1999) [Pubmed]
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