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Ccr3  -  chemokine (C-C motif) receptor 3

Mus musculus

Synonyms: C-C CKR-3, CC-CKR-3, CC-CKR3, CCR-3, CCR3, ...
 
 
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Disease relevance of Ccr3

  • Aim: To explore the effect of a rat anti-mouse CC-chemokine receptor-3 (CCR3) monoclonal antibody (CCR3 mAb) on airway eosinophilia and mucus overproduction in asthmatic mice [1].
  • These results imply that successful blockade of Ag-induced pulmonary eosinophilia will require antagonism of multiple CCR3 ligands [2].
  • Increased expression of CCR3 but not CCR10 could be detected during the induction of the CRA-induced pulmonary inflammation [3].
  • Transcripts for eotaxin, IL-4, and CCR3 (eotaxin receptor) were also enhanced during type 2 granuloma formation [4].
  • Functional inhibition of CCR3-dependent responses by peptides derived from phage libraries [5].
 

High impact information on Ccr3

 

Chemical compound and disease context of Ccr3

  • The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia [2].
  • Analysis of airway (luminal) eosinophilia revealed a dominant role for eotaxin-2 and a synergistic reduction in eotaxin-1/2 double-deficient (DKO) and CCR3-deficient mice [2].
  • The present study examined the pulmonary expression of CCL11 and CCR3 during bleomycin (blm)-induced lung injury and determined their importance in the recruitment of inflammatory cells and the development of lung fibrosis [8].
 

Biological context of Ccr3

  • KA treatment did not affect CCR3 mRNA expression in the wild-type mice, whereas KO mice showed both a higher basal level of CCR3 mRNA expression as well as a strong upregulation following KA treatment [9].
  • To examine receptor/ligand interactions in more detail, we performed alanine scanning mutagenesis of 21 charged residues within the extracellular loops (ECLs) of CCR3 [10].
  • Asthmatic mice were given dual administration (intraperitoneal injection and aerosol inhalation) of CCR3 mAb or nonspecific rat IgG (ns-IgG) [1].
  • CCR1 and CCR3 are 54% identical in amino acid sequence and share some ligands but not others [11].
  • The peptide inhibited chemotaxis of CCR3 transfectants induced by a broad panel of CCR3 ligands [5].
 

Anatomical context of Ccr3

 

Associations of Ccr3 with chemical compounds

  • The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic acid-induced hippocampal injury: evidence for a compensatory effect by increased CCR2 and CCR3 [9].
  • Notably, the organized accumulation of eosinophils in the peribronchial and perivascular regions of allergen-challenged wild-type mice was lost in eotaxin-1/2 DKO and CCR3-deficient mice [2].
  • Furthermore, it had weak agonistic effects on Ca(2+) mobilization in CCR3 transfectants that underwent heterologous desensitization by subsequent exposure to eotaxin [5].
  • CXCR4 expression was completely attenuated by IL-4 and IL-5 and upregulated by IFN-gamma and dexamethasone, while CCR3 expression was only marginally affected [15].
  • Additionally, mAbs were raised against macaque CCR3 using two different immunogens: a 30-amino acid synthetic peptide derived from the predicted NH(2) terminus of macaque CCR3 and intact macaque CCR3-transfected cells [16].
  • Mutation of the residue Tyr-113 to alanine was found to turn the antagonist UCB35625 into a CCR3 agonist [17].
 

Regulatory relationships of Ccr3

 

Other interactions of Ccr3

  • Alanine scanning mutagenesis of the chemokine receptor CCR3 reveals distinct extracellular residues involved in recognition of the eotaxin family of chemokines [10].
  • The chemokine CCL11 is agonist for the chemokine receptor CCR3 and acts in synergy with IL-5 to recruit eosinophils to inflammatory sites [19].
  • Agents that bind to the N-terminal segments of CCR1 and CCR3 may be useful in blocking receptor function [11].
  • Transcripts for CCR3 and CCR6, receptors that are not highly expressed on activated T cells or macrophages, also appeared to be induced during acute and latent phases; however, their very low expression levels were near the limit of our detection [20].
  • Association of CD45(dim)VLA-4 (+) cells with the NKT cell lineage and their selective expression of IL-13, IP-15, and CCR3 transcripts [21].
 

Analytical, diagnostic and therapeutic context of Ccr3

References

  1. CCR3 monoclonal antibody inhibits airway eosinophilic inflammation and mucus overproduction in a mouse model of asthma. Shen, H.H., Xu, F., Zhang, G.S., Wang, S.B., Xu, W.H. Acta Pharmacol. Sin. (2006) [Pubmed]
  2. The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. Pope, S.M., Zimmermann, N., Stringer, K.F., Karow, M.L., Rothenberg, M.E. J. Immunol. (2005) [Pubmed]
  3. Temporal production of CCL28 corresponds to eosinophil accumulation and airway hyperreactivity in allergic airway inflammation. John, A.E., Thomas, M.S., Berlin, A.A., Lukacs, N.W. Am. J. Pathol. (2005) [Pubmed]
  4. Expression and participation of eotaxin during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granuloma formation. Ruth, J.H., Lukacs, N.W., Warmington, K.S., Polak, T.J., Burdick, M., Kunkel, S.L., Strieter, R.M., Chensue, S.W. J. Immunol. (1998) [Pubmed]
  5. Functional inhibition of CCR3-dependent responses by peptides derived from phage libraries. Houimel, M., Loetscher, P., Baggiolini, M., Mazzucchelli, L. Eur. J. Immunol. (2001) [Pubmed]
  6. CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. Ma, W., Bryce, P.J., Humbles, A.A., Laouini, D., Yalcindag, A., Alenius, H., Friend, D.S., Oettgen, H.C., Gerard, C., Geha, R.S. J. Clin. Invest. (2002) [Pubmed]
  7. Lymph node trafficking and antigen presentation by endobronchial eosinophils. Shi, H.Z., Humbles, A., Gerard, C., Jin, Z., Weller, P.F. J. Clin. Invest. (2000) [Pubmed]
  8. Role of Eotaxin-1 (CCL11) and CC chemokine receptor 3 (CCR3) in bleomycin-induced lung injury and fibrosis. Huaux, F., Gharaee-Kermani, M., Liu, T., Morel, V., McGarry, B., Ullenbruch, M., Kunkel, S.L., Wang, J., Xing, Z., Phan, S.H. Am. J. Pathol. (2005) [Pubmed]
  9. The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic acid-induced hippocampal injury: evidence for a compensatory effect by increased CCR2 and CCR3. Chen, Z., Yu, S., Bakhiet, M., Winblad, B., Zhu, J. J. Neurochem. (2003) [Pubmed]
  10. Alanine scanning mutagenesis of the chemokine receptor CCR3 reveals distinct extracellular residues involved in recognition of the eotaxin family of chemokines. Duchesnes, C.E., Murphy, P.M., Williams, T.J., Pease, J.E. Mol. Immunol. (2006) [Pubmed]
  11. The N-terminal extracellular segments of the chemokine receptors CCR1 and CCR3 are determinants for MIP-1alpha and eotaxin binding, respectively, but a second domain is essential for efficient receptor activation. Pease, J.E., Wang, J., Ponath, P.D., Murphy, P.M. J. Biol. Chem. (1998) [Pubmed]
  12. LPS induces eosinophil migration via CCR3 signaling through a mechanism independent of RANTES and Eotaxin. Penido, C., Castro-Faria-Neto, H.C., Vieira-de-Abreu, A., Figueiredo, R.T., Pelled, A., Martins, M.A., Jose, P.J., Williams, T.J., Bozza, P.T. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  13. Eotaxin influences the development of embryonic hematopoietic progenitors in the mouse. Quackenbush, E.J., Aguirre, V., Wershil, B.K., Gutierrez-Ramos, J.C. J. Leukoc. Biol. (1997) [Pubmed]
  14. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Humbles, A.A., Lu, B., Friend, D.S., Okinaga, S., Lora, J., Al-Garawi, A., Martin, T.R., Gerard, N.P., Gerard, C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  15. Regulation of chemokine receptor expression in eosinophils. Nagase, H., Miyamasu, M., Yamaguchi, M., Fujisawa, T., Kawasaki, H., Ohta, K., Yamamoto, K., Morita, Y., Hirai, K. Int. Arch. Allergy Immunol. (2001) [Pubmed]
  16. Functional expression and characterization of macaque C-C chemokine receptor 3 (CCR3) and generation of potent antagonistic anti-macaque CCR3 monoclonal antibodies. Zhang, L., Soares, M.P., Guan, Y., Matheravidathu, S., Wnek, R., Johnson, K.E., Meisher, A., Iliff, S.A., Mudgett, J.S., Springer, M.S., Daugherty, B.L. J. Biol. Chem. (2002) [Pubmed]
  17. Small molecule receptor agonists and antagonists of CCR3 provide insight into mechanisms of chemokine receptor activation. Wise, E.L., Duchesnes, C., da Fonseca, P.C., Allen, R.A., Williams, T.J., Pease, J.E. J. Biol. Chem. (2007) [Pubmed]
  18. CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism. Fulkerson, P.C., Zhu, H., Williams, D.A., Zimmermann, N., Rothenberg, M.E. Blood (2005) [Pubmed]
  19. The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection. Dixon, H., Blanchard, C., Deschoolmeester, M.L., Yuill, N.C., Christie, J.W., Rothenberg, M.E., Else, K.J. Eur. J. Immunol. (2006) [Pubmed]
  20. Persistent expression of chemokine and chemokine receptor RNAs at primary and latent sites of herpes simplex virus 1 infection. Cook, W.J., Kramer, M.F., Walker, R.M., Burwell, T.J., Holman, H.A., Coen, D.M., Knipe, D.M. Virol. J. (2004) [Pubmed]
  21. Association of CD45(dim)VLA-4 (+) cells with the NKT cell lineage and their selective expression of IL-13, IP-15, and CCR3 transcripts. Matejuk, A., Afentoulis, M. Arch. Immunol. Ther. Exp. (Warsz.) (2006) [Pubmed]
  22. CCR3-blocking antibody inhibits allergen-induced eosinophil recruitment in human skin xenografts from allergic patients. Sénéchal, S., Fahy, O., Gentina, T., Vorng, H., Capron, M., Walls, A.F., McEuen, A.R., Buckley, M.G., Hamid, Q., Wallaert, B., Tonnel, A.B., Tsicopoulos, A. Lab. Invest. (2002) [Pubmed]
  23. The CCR3 receptor is involved in eosinophil differentiation and is up-regulated by Th2 cytokines in CD34+ progenitor cells. Lamkhioued, B., Abdelilah, S.G., Hamid, Q., Mansour, N., Delespesse, G., Renzi, P.M. J. Immunol. (2003) [Pubmed]
  24. Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localizing with eosinophils. Gerber, B.O., Zanni, M.P., Uguccioni, M., Loetscher, M., Mackay, C.R., Pichler, W.J., Yawalkar, N., Baggiolini, M., Moser, B. Curr. Biol. (1997) [Pubmed]
  25. Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency. De Lucca, G.V., Kim, U.T., Vargo, B.J., Duncia, J.V., Santella, J.B., Gardner, D.S., Zheng, C., Liauw, A., Wang, Z., Emmett, G., Wacker, D.A., Welch, P.K., Covington, M., Stowell, N.C., Wadman, E.A., Das, A.M., Davies, P., Yeleswaram, S., Graden, D.M., Solomon, K.A., Newton, R.C., Trainor, G.L., Decicco, C.P., Ko, S.S. J. Med. Chem. (2005) [Pubmed]
 
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