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Ccr2  -  chemokine (C-C motif) receptor 2

Rattus norvegicus

Synonyms: C-C CKR-2, C-C chemokine receptor type 2, CC-CKR-2, CCR-2, CCR2, ...
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Disease relevance of Ccr2

  • A 2-fold increase in the number of mononuclear cells that express CCR2 was also found in rats with orchitis compared with controls [1].
  • The histopathological analysis of tissues from the delayed-type hypersensitivity model demonstrates that inhibition of CCR2 leads to a substantial reduction in tissue inflammation, suggesting that macrophages play an orchestrating role in immune-based inflammatory reactions [2].
  • Recent studies demonstrated that the chemokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 and its receptor, CCR2, play important roles in various brain diseases [3].
  • We used a reproducible model of focal excitotoxic brain injury elicited by intrahippocampal injection of NMDA (10 nmol) in 7-day-old rats, to examine injury-induced alterations in MCP-1 and CCR2 expression [4].
  • These results demonstrate that CCR2 expression is markedly upregulated in this brain tumor model [5].

High impact information on Ccr2

  • Flow cytometry revealed novel expression of the CC chemokine receptors CCR1 and CCR2 on neutrophils from adjuvant-immunized animals [6].
  • MCP-1/CCR2 signaling is directly involved with a chronic compression injury and may contribute to associated neuronal hyperexcitability and neuropathic pain [7].
  • Using a neuropathic pain model, chronic compression of the DRG (CCD), we compared anatomically separate populations of noncompressed lumbar DRG (L3/L6) with compressed lumbar DRG (L4/L5) for changes in the gene expression of CCR2 [7].
  • Endothelial cell (EC) CCR2 was down-regulated as arthritis progressed, inversely correlating with inflammation [8].
  • At baseline, primed macrophages expressed a small subset of IFN-gamma-inducible genes, including CCR2, and exhibited increased migration in response to CCL2 [9].

Chemical compound and disease context of Ccr2


Biological context of Ccr2


Anatomical context of Ccr2


Associations of Ccr2 with chemical compounds

  • Because arterial angiotensin II, which induces MCP-1 expression, increases with age, we hypothesized that aortic MCP-1 and its receptor CCR2 are also upregulated and affect VSMC properties [17].
  • Inhibition of the CCR2-mediated inflammation may represent novel antiinflammatory actions of pioglitazone beyond improvement of metabolic state [10].
  • CCR2 deficiency has the same effect as blockade of all CC chemokines [11].
  • Treatment of 21 normocholesterolemic men with simvastatin (20 mg/d for 2 weeks) decreased CCR2 protein and mRNA expression in circulating monocytes [18].
  • Enhanced CCR2 intensity on monocytes was observed in hypertensive patients and rats, and was reduced by treatment with the Ang II receptor blocker, supporting the clinical relevance of the observation in mice [12].

Physical interactions of Ccr2


Other interactions of Ccr2


Analytical, diagnostic and therapeutic context of Ccr2

  • In situ hybridization revealed that CCR2 mRNA was up-regulated in neurons and nonneuronal cells present in both compressed L4/L5 and ipsilateral noncompressed L3/L6 DRGs at postoperative day 5 (POD5) [7].
  • These data are largely in accordance with results obtained using quantitative autoradiography with [(125)I]MCP-1/CCL2 and RT-PCR CCR2 mRNA analysis [13].
  • In this work, using a semiquantitative immunohistochemistry approach, we provide the first neuroanatomical mapping of constitutive neuronal CCR2 localization [13].
  • RT-PCR analysis showed high levels of both MCP-1 and CCR2 mRNA and Western blot analysis demonstrated increased CCR2 protein in tumor extracts [5].
  • Expression of the MCP-1 receptor CCR2 in neurosphere cultures was verified by RT-PCR and immunofluorescence microscopy [20].


  1. Monocyte chemoattractant protein-1 (MCP-1/CCL2) in experimental autoimmune orchitis. Guazzone, V.A., Rival, C., Denduchis, B., Lustig, L. J. Reprod. Immunol. (2003) [Pubmed]
  2. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. Brodmerkel, C.M., Huber, R., Covington, M., Diamond, S., Hall, L., Collins, R., Leffet, L., Gallagher, K., Feldman, P., Collier, P., Stow, M., Gu, X., Baribaud, F., Shin, N., Thomas, B., Burn, T., Hollis, G., Yeleswaram, S., Solomon, K., Friedman, S., Wang, A., Xue, C.B., Newton, R.C., Scherle, P., Vaddi, K. J. Immunol. (2005) [Pubmed]
  3. Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain. Banisadr, G., Quéraud-Lesaux, F., Boutterin, M.C., Pélaprat, D., Zalc, B., Rostène, W., Haour, F., Parsadaniantz, S.M. J. Neurochem. (2002) [Pubmed]
  4. Acute excitotoxic injury induces expression of monocyte chemoattractant protein-1 and its receptor, CCR2, in neonatal rat brain. Galasso, J.M., Miller, M.J., Cowell, R.M., Harrison, J.K., Warren, J.S., Silverstein, F.S. Exp. Neurol. (2000) [Pubmed]
  5. Experimental gliosarcoma induces chemokine receptor expression in rat brain. Galasso, J.M., Stegman, L.D., Blaivas, M., Harrison, J.K., Ross, B.D., Silverstein, F.S. Exp. Neurol. (2000) [Pubmed]
  6. Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. Johnston, B., Burns, A.R., Suematsu, M., Issekutz, T.B., Woodman, R.C., Kubes, P. J. Clin. Invest. (1999) [Pubmed]
  7. Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion. White, F.A., Sun, J., Waters, S.M., Ma, C., Ren, D., Ripsch, M., Steflik, J., Cortright, D.N., Lamotte, R.H., Miller, R.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Chemokine receptor expression in rat adjuvant-induced arthritis. Haas, C.S., Martinez, R.J., Attia, N., Haines, G.K., Campbell, P.L., Koch, A.E. Arthritis Rheum. (2005) [Pubmed]
  9. IFN-gamma-primed macrophages exhibit increased CCR2-dependent migration and altered IFN-gamma responses mediated by Stat1. Hu, X., Park-Min, K.H., Ho, H.H., Ivashkiv, L.B. J. Immunol. (2005) [Pubmed]
  10. Antiinflammatory and antiarteriosclerotic effects of pioglitazone. Ishibashi, M., Egashira, K., Hiasa, K., Inoue, S., Ni, W., Zhao, Q., Usui, M., Kitamoto, S., Ichiki, T., Takeshita, A. Hypertension (2002) [Pubmed]
  11. Monocyte recruitment in venous thrombus resolution. Ali, T., Humphries, J., Burnand, K., Sawyer, B., Bursill, C., Channon, K., Greaves, D., Rollins, B., Charo, I.F., Smith, A. J. Vasc. Surg. (2006) [Pubmed]
  12. Critical role of monocyte chemoattractant protein-1 receptor CCR2 on monocytes in hypertension-induced vascular inflammation and remodeling. Ishibashi, M., Hiasa, K., Zhao, Q., Inoue, S., Ohtani, K., Kitamoto, S., Tsuchihashi, M., Sugaya, T., Charo, I.F., Kura, S., Tsuzuki, T., Ishibashi, T., Takeshita, A., Egashira, K. Circ. Res. (2004) [Pubmed]
  13. Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: functional effect of MCP-1/CCL2 on calcium mobilization in primary cultured neurons. Banisadr, G., Gosselin, R.D., Mechighel, P., Rostène, W., Kitabgi, P., Mélik Parsadaniantz, S. J. Comp. Neurol. (2005) [Pubmed]
  14. Chemokine receptor expression and in vivo signaling pathways in the joints of rats with adjuvant-induced arthritis. Shahrara, S., Amin, M.A., Woods, J.M., Haines, G.K., Koch, A.E. Arthritis Rheum. (2003) [Pubmed]
  15. Novel, orally bioavailable gamma-aminoamide CC chemokine receptor 2 (CCR2) antagonists. Pasternak, A., Marino, D., Vicario, P.P., Ayala, J.M., Cascierri, M.A., Parsons, W., Mills, S.G., Maccoss, M., Yang, L. J. Med. Chem. (2006) [Pubmed]
  16. Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis. Kataoka, C., Egashira, K., Ishibashi, M., Inoue, S., Ni, W., Hiasa, K., Kitamoto, S., Usui, M., Takeshita, A. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  17. Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function. Spinetti, G., Wang, M., Monticone, R., Zhang, J., Zhao, D., Lakatta, E.G. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  18. HMG-CoA reductase inhibition reduces monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated monocyte recruitment in vivo. Han, K.H., Ryu, J., Hong, K.H., Ko, J., Pak, Y.K., Kim, J.B., Park, S.W., Kim, J.J. Circulation (2005) [Pubmed]
  19. Kinetics of chemokines and their receptors in mercuric chloride-induced tubulointerstitial lesions in brown Norway rats. Suzuki, K., Kanabayashi, T., Nakayama, H., Doi, K. Exp. Mol. Pathol. (2003) [Pubmed]
  20. MCP-1 induces migration of adult neural stem cells. Widera, D., Holtkamp, W., Entschladen, F., Niggemann, B., Zänker, K., Kaltschmidt, B., Kaltschmidt, C. Eur. J. Cell Biol. (2004) [Pubmed]
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