Cloning and functional characterization of the rabbit C-C chemokine receptor 2
<p>Abstract</p> <p>Background</p> <p>CC-family chemokine receptor 2 (CCR2) is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2005-07-01
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| Series: | BMC Immunology |
| Online Access: | http://www.biomedcentral.com/1471-2172/6/15 |
| _version_ | 1811284786063343616 |
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| author | Hamdouchi Chafiq Su Eric W Wang He Pappas Amy T Evans Robert J Yuan Xiu-juan Lu Deshun Venkataraman Chandrasekar |
| author_facet | Hamdouchi Chafiq Su Eric W Wang He Pappas Amy T Evans Robert J Yuan Xiu-juan Lu Deshun Venkataraman Chandrasekar |
| author_sort | Hamdouchi Chafiq |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>CC-family chemokine receptor 2 (CCR2) is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. The major challenge in the development of small molecule chemokine receptor antagonists is the lack of cross-species activity to the receptor in the preclinical species. Rabbit models have been widely used to study the role of various inflammatory molecules in the development of inflammatory processes. Therefore, in this study, we report the cloning and characterization of rabbit CCR2. Data regarding the activity of the CCR2 antagonist will provide valuable tools to perform toxicology and efficacy studies in the rabbit model.</p> <p>Results</p> <p>Sequence alignment indicated that rabbit CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2 expressed as stable transfectants in U-937 cells binds radiolabeled <sup>125</sup>I-mouse JE (murine MCP-1) with a calculated <it>K</it><sub><it>d </it></sub>of 0.1 nM. In competition binding assays, binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1α or MIP-1β. U-937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b. Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of <sup>125</sup>I-mouse JE (<it>IC</it><sub>50 </sub>= 2.3 nM) to rabbit CCR2 and effectively blocks CCR2-mediated chemotaxis.</p> <p>Conclusion</p> <p>In this study, we report the cloning of rabbit CCR2 and demonstrate that this receptor is a functional chemotactic receptor for MCP-1.</p> |
| first_indexed | 2024-04-13T02:34:00Z |
| format | Article |
| id | doaj.art-6b98d3730824499fbf5f8399d378fc9a |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-04-13T02:34:00Z |
| publishDate | 2005-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-6b98d3730824499fbf5f8399d378fc9a2022-12-22T03:06:26ZengBMCBMC Immunology1471-21722005-07-01611510.1186/1471-2172-6-15Cloning and functional characterization of the rabbit C-C chemokine receptor 2Hamdouchi ChafiqSu Eric WWang HePappas Amy TEvans Robert JYuan Xiu-juanLu DeshunVenkataraman Chandrasekar<p>Abstract</p> <p>Background</p> <p>CC-family chemokine receptor 2 (CCR2) is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. The major challenge in the development of small molecule chemokine receptor antagonists is the lack of cross-species activity to the receptor in the preclinical species. Rabbit models have been widely used to study the role of various inflammatory molecules in the development of inflammatory processes. Therefore, in this study, we report the cloning and characterization of rabbit CCR2. Data regarding the activity of the CCR2 antagonist will provide valuable tools to perform toxicology and efficacy studies in the rabbit model.</p> <p>Results</p> <p>Sequence alignment indicated that rabbit CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2 expressed as stable transfectants in U-937 cells binds radiolabeled <sup>125</sup>I-mouse JE (murine MCP-1) with a calculated <it>K</it><sub><it>d </it></sub>of 0.1 nM. In competition binding assays, binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1α or MIP-1β. U-937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b. Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of <sup>125</sup>I-mouse JE (<it>IC</it><sub>50 </sub>= 2.3 nM) to rabbit CCR2 and effectively blocks CCR2-mediated chemotaxis.</p> <p>Conclusion</p> <p>In this study, we report the cloning of rabbit CCR2 and demonstrate that this receptor is a functional chemotactic receptor for MCP-1.</p>http://www.biomedcentral.com/1471-2172/6/15 |
| spellingShingle | Hamdouchi Chafiq Su Eric W Wang He Pappas Amy T Evans Robert J Yuan Xiu-juan Lu Deshun Venkataraman Chandrasekar Cloning and functional characterization of the rabbit C-C chemokine receptor 2 BMC Immunology |
| title | Cloning and functional characterization of the rabbit C-C chemokine receptor 2 |
| title_full | Cloning and functional characterization of the rabbit C-C chemokine receptor 2 |
| title_fullStr | Cloning and functional characterization of the rabbit C-C chemokine receptor 2 |
| title_full_unstemmed | Cloning and functional characterization of the rabbit C-C chemokine receptor 2 |
| title_short | Cloning and functional characterization of the rabbit C-C chemokine receptor 2 |
| title_sort | cloning and functional characterization of the rabbit c c chemokine receptor 2 |
| url | http://www.biomedcentral.com/1471-2172/6/15 |
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