Inhibition of CXCR3‐mediated chemotaxis by the human chemokine receptor‐like protein CCX‐CKR
Background and Purpose Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor‐like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine s...
Gespeichert in:
| Veröffentlicht in: | British journal of pharmacology 2013-03, Vol.168 (6), p.1375-1387 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1387 |
|---|---|
| container_issue | 6 |
| container_start_page | 1375 |
| container_title | British journal of pharmacology |
| container_volume | 168 |
| creator | Vinet, J Zwam, M Dijkstra, IM Brouwer, N Weering, HRJ Watts, A Meijer, M Fokkens, MR Kannan, V Verzijl, D Vischer, HF Smit, MJ Leurs, R Biber, K Boddeke, HWGM |
| description | Background and Purpose
Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor‐like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine scavengers, which may control local chemokine levels and contribute to the function of chemokines during inflammation. This has been verified for the chemokine‐like receptor proteins D6 and DARC as well as CCX‐CKR. Here, we provide evidence for an additional biological function of human (h)CCX‐CKR.
Experimental Approach
We used transfection strategies in HEK293 and human T cells.
Key Results
Co‐expression of hCCX‐CKR completely inhibits hCXCR3‐induced chemotaxis. We found that hCCX‐CKR forms complexes with hCXCR3, suggesting a relationship between CCX‐CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding cooperativity induced by ligands both for hCXCR3 and hCCX‐CKR was observed in cells expressing both receptors. This negative cooperativity may also explain the hCCX‐CKR‐induced inhibition of chemotaxis.
Conclusions and Implications
These findings suggest that hCCX‐CKR prevents hCXCR3‐induced chemotaxis by heteromerization thus representing a novel mechanism of regulation of immune cell migration. |
| doi_str_mv | 10.1111/bph.12042 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3596643</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3315988611</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5092-9c52089172bb9717ec7ba46094a30c79971a96c9847e429db48ecd09a8bddd1c3</originalsourceid><addsrcrecordid>eNp1kU1u1TAUhS0Eoo_CgA0gS0xgkNZ2_BNPkCAqtKISqAKpM8t27iNukzh1EsqbsQTWyEowpFSAhCeWzv18dK4PQo8pOaD5HLqxPaCMcHYHbShXshBlRe-iDSFEFZRW1R56ME0XhOShEvfRHispo0KoDXInQxtcmEMccNzi-rw-K79__dZDE-wMDfYt9HG2X8KE3Q7PLeB26e2w6pdhAJzAwzjHlF914RLwmOIMYcB1fZ6l-u3ZQ3Rva7sJHt3c--jj66MP9XFx-u7NSf3ytPCCaFZoLxipNFXMOa2oAq-c5ZJobkvilc6a1dLriivgTDeOV-Abom3lmqahvtxHL1bfcXE5v4dhTrYzYwq9TTsTbTB_T4bQmk_xsymFlpKX2eDZjUGKVwtMs-nD5KHr7ABxmQzNvyYlE4Jn9Ok_6EVc0pDXM1SwStJKlixTz1fKpzhNCba3YSgxP5szuTnzq7nMPvkz_S35u6oMHK7Adehg938n8-r98Wr5A-hNpRM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1528618632</pqid></control><display><type>article</type><title>Inhibition of CXCR3‐mediated chemotaxis by the human chemokine receptor‐like protein CCX‐CKR</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Online Library Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Vinet, J ; Zwam, M ; Dijkstra, IM ; Brouwer, N ; Weering, HRJ ; Watts, A ; Meijer, M ; Fokkens, MR ; Kannan, V ; Verzijl, D ; Vischer, HF ; Smit, MJ ; Leurs, R ; Biber, K ; Boddeke, HWGM</creator><creatorcontrib>Vinet, J ; Zwam, M ; Dijkstra, IM ; Brouwer, N ; Weering, HRJ ; Watts, A ; Meijer, M ; Fokkens, MR ; Kannan, V ; Verzijl, D ; Vischer, HF ; Smit, MJ ; Leurs, R ; Biber, K ; Boddeke, HWGM</creatorcontrib><description>Background and Purpose
Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor‐like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine scavengers, which may control local chemokine levels and contribute to the function of chemokines during inflammation. This has been verified for the chemokine‐like receptor proteins D6 and DARC as well as CCX‐CKR. Here, we provide evidence for an additional biological function of human (h)CCX‐CKR.
Experimental Approach
We used transfection strategies in HEK293 and human T cells.
Key Results
Co‐expression of hCCX‐CKR completely inhibits hCXCR3‐induced chemotaxis. We found that hCCX‐CKR forms complexes with hCXCR3, suggesting a relationship between CCX‐CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding cooperativity induced by ligands both for hCXCR3 and hCCX‐CKR was observed in cells expressing both receptors. This negative cooperativity may also explain the hCCX‐CKR‐induced inhibition of chemotaxis.
Conclusions and Implications
These findings suggest that hCCX‐CKR prevents hCXCR3‐induced chemotaxis by heteromerization thus representing a novel mechanism of regulation of immune cell migration.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/bph.12042</identifier><identifier>PMID: 23121557</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Cell adhesion & migration ; Cells, Cultured ; chemokine receptors ; Chemokines ; Chemokines - metabolism ; Chemotaxis, Leukocyte ; Down-Regulation ; Fluorescence Resonance Energy Transfer ; Gene Expression Regulation ; HEK293 Cells ; heteromerization ; Humans ; Immunohistochemistry ; Kinetics ; Ligands ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Protein Multimerization ; Protein Transport ; Receptors, CCR - genetics ; Receptors, CCR - metabolism ; Receptors, CXCR3 - genetics ; Receptors, CXCR3 - metabolism ; Recombinant Fusion Proteins - metabolism ; Recombinant Proteins - metabolism ; Research Papers ; RNA, Messenger ; T cells ; T-Lymphocytes - cytology ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism</subject><ispartof>British journal of pharmacology, 2013-03, Vol.168 (6), p.1375-1387</ispartof><rights>2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society</rights><rights>2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.</rights><rights>British Journal of Pharmacology © 2013 The British Pharmacological Society</rights><rights>British Journal of Pharmacology © 2013 The British Pharmacological Society 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5092-9c52089172bb9717ec7ba46094a30c79971a96c9847e429db48ecd09a8bddd1c3</citedby><cites>FETCH-LOGICAL-c5092-9c52089172bb9717ec7ba46094a30c79971a96c9847e429db48ecd09a8bddd1c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596643/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596643/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23121557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vinet, J</creatorcontrib><creatorcontrib>Zwam, M</creatorcontrib><creatorcontrib>Dijkstra, IM</creatorcontrib><creatorcontrib>Brouwer, N</creatorcontrib><creatorcontrib>Weering, HRJ</creatorcontrib><creatorcontrib>Watts, A</creatorcontrib><creatorcontrib>Meijer, M</creatorcontrib><creatorcontrib>Fokkens, MR</creatorcontrib><creatorcontrib>Kannan, V</creatorcontrib><creatorcontrib>Verzijl, D</creatorcontrib><creatorcontrib>Vischer, HF</creatorcontrib><creatorcontrib>Smit, MJ</creatorcontrib><creatorcontrib>Leurs, R</creatorcontrib><creatorcontrib>Biber, K</creatorcontrib><creatorcontrib>Boddeke, HWGM</creatorcontrib><title>Inhibition of CXCR3‐mediated chemotaxis by the human chemokine receptor‐like protein CCX‐CKR</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Background and Purpose
Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor‐like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine scavengers, which may control local chemokine levels and contribute to the function of chemokines during inflammation. This has been verified for the chemokine‐like receptor proteins D6 and DARC as well as CCX‐CKR. Here, we provide evidence for an additional biological function of human (h)CCX‐CKR.
Experimental Approach
We used transfection strategies in HEK293 and human T cells.
Key Results
Co‐expression of hCCX‐CKR completely inhibits hCXCR3‐induced chemotaxis. We found that hCCX‐CKR forms complexes with hCXCR3, suggesting a relationship between CCX‐CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding cooperativity induced by ligands both for hCXCR3 and hCCX‐CKR was observed in cells expressing both receptors. This negative cooperativity may also explain the hCCX‐CKR‐induced inhibition of chemotaxis.
Conclusions and Implications
These findings suggest that hCCX‐CKR prevents hCXCR3‐induced chemotaxis by heteromerization thus representing a novel mechanism of regulation of immune cell migration.</description><subject>Cell adhesion & migration</subject><subject>Cells, Cultured</subject><subject>chemokine receptors</subject><subject>Chemokines</subject><subject>Chemokines - metabolism</subject><subject>Chemotaxis, Leukocyte</subject><subject>Down-Regulation</subject><subject>Fluorescence Resonance Energy Transfer</subject><subject>Gene Expression Regulation</subject><subject>HEK293 Cells</subject><subject>heteromerization</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kinetics</subject><subject>Ligands</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Protein Multimerization</subject><subject>Protein Transport</subject><subject>Receptors, CCR - genetics</subject><subject>Receptors, CCR - metabolism</subject><subject>Receptors, CXCR3 - genetics</subject><subject>Receptors, CXCR3 - metabolism</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Recombinant Proteins - metabolism</subject><subject>Research Papers</subject><subject>RNA, Messenger</subject><subject>T cells</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1u1TAUhS0Eoo_CgA0gS0xgkNZ2_BNPkCAqtKISqAKpM8t27iNukzh1EsqbsQTWyEowpFSAhCeWzv18dK4PQo8pOaD5HLqxPaCMcHYHbShXshBlRe-iDSFEFZRW1R56ME0XhOShEvfRHispo0KoDXInQxtcmEMccNzi-rw-K79__dZDE-wMDfYt9HG2X8KE3Q7PLeB26e2w6pdhAJzAwzjHlF914RLwmOIMYcB1fZ6l-u3ZQ3Rva7sJHt3c--jj66MP9XFx-u7NSf3ytPCCaFZoLxipNFXMOa2oAq-c5ZJobkvilc6a1dLriivgTDeOV-Abom3lmqahvtxHL1bfcXE5v4dhTrYzYwq9TTsTbTB_T4bQmk_xsymFlpKX2eDZjUGKVwtMs-nD5KHr7ABxmQzNvyYlE4Jn9Ok_6EVc0pDXM1SwStJKlixTz1fKpzhNCba3YSgxP5szuTnzq7nMPvkz_S35u6oMHK7Adehg938n8-r98Wr5A-hNpRM</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>Vinet, J</creator><creator>Zwam, M</creator><creator>Dijkstra, IM</creator><creator>Brouwer, N</creator><creator>Weering, HRJ</creator><creator>Watts, A</creator><creator>Meijer, M</creator><creator>Fokkens, MR</creator><creator>Kannan, V</creator><creator>Verzijl, D</creator><creator>Vischer, HF</creator><creator>Smit, MJ</creator><creator>Leurs, R</creator><creator>Biber, K</creator><creator>Boddeke, HWGM</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201303</creationdate><title>Inhibition of CXCR3‐mediated chemotaxis by the human chemokine receptor‐like protein CCX‐CKR</title><author>Vinet, J ; Zwam, M ; Dijkstra, IM ; Brouwer, N ; Weering, HRJ ; Watts, A ; Meijer, M ; Fokkens, MR ; Kannan, V ; Verzijl, D ; Vischer, HF ; Smit, MJ ; Leurs, R ; Biber, K ; Boddeke, HWGM</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5092-9c52089172bb9717ec7ba46094a30c79971a96c9847e429db48ecd09a8bddd1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Cell adhesion & migration</topic><topic>Cells, Cultured</topic><topic>chemokine receptors</topic><topic>Chemokines</topic><topic>Chemokines - metabolism</topic><topic>Chemotaxis, Leukocyte</topic><topic>Down-Regulation</topic><topic>Fluorescence Resonance Energy Transfer</topic><topic>Gene Expression Regulation</topic><topic>HEK293 Cells</topic><topic>heteromerization</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kinetics</topic><topic>Ligands</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Protein Multimerization</topic><topic>Protein Transport</topic><topic>Receptors, CCR - genetics</topic><topic>Receptors, CCR - metabolism</topic><topic>Receptors, CXCR3 - genetics</topic><topic>Receptors, CXCR3 - metabolism</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Recombinant Proteins - metabolism</topic><topic>Research Papers</topic><topic>RNA, Messenger</topic><topic>T cells</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vinet, J</creatorcontrib><creatorcontrib>Zwam, M</creatorcontrib><creatorcontrib>Dijkstra, IM</creatorcontrib><creatorcontrib>Brouwer, N</creatorcontrib><creatorcontrib>Weering, HRJ</creatorcontrib><creatorcontrib>Watts, A</creatorcontrib><creatorcontrib>Meijer, M</creatorcontrib><creatorcontrib>Fokkens, MR</creatorcontrib><creatorcontrib>Kannan, V</creatorcontrib><creatorcontrib>Verzijl, D</creatorcontrib><creatorcontrib>Vischer, HF</creatorcontrib><creatorcontrib>Smit, MJ</creatorcontrib><creatorcontrib>Leurs, R</creatorcontrib><creatorcontrib>Biber, K</creatorcontrib><creatorcontrib>Boddeke, HWGM</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vinet, J</au><au>Zwam, M</au><au>Dijkstra, IM</au><au>Brouwer, N</au><au>Weering, HRJ</au><au>Watts, A</au><au>Meijer, M</au><au>Fokkens, MR</au><au>Kannan, V</au><au>Verzijl, D</au><au>Vischer, HF</au><au>Smit, MJ</au><au>Leurs, R</au><au>Biber, K</au><au>Boddeke, HWGM</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of CXCR3‐mediated chemotaxis by the human chemokine receptor‐like protein CCX‐CKR</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2013-03</date><risdate>2013</risdate><volume>168</volume><issue>6</issue><spage>1375</spage><epage>1387</epage><pages>1375-1387</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>Background and Purpose
Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor‐like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine scavengers, which may control local chemokine levels and contribute to the function of chemokines during inflammation. This has been verified for the chemokine‐like receptor proteins D6 and DARC as well as CCX‐CKR. Here, we provide evidence for an additional biological function of human (h)CCX‐CKR.
Experimental Approach
We used transfection strategies in HEK293 and human T cells.
Key Results
Co‐expression of hCCX‐CKR completely inhibits hCXCR3‐induced chemotaxis. We found that hCCX‐CKR forms complexes with hCXCR3, suggesting a relationship between CCX‐CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding cooperativity induced by ligands both for hCXCR3 and hCCX‐CKR was observed in cells expressing both receptors. This negative cooperativity may also explain the hCCX‐CKR‐induced inhibition of chemotaxis.
Conclusions and Implications
These findings suggest that hCCX‐CKR prevents hCXCR3‐induced chemotaxis by heteromerization thus representing a novel mechanism of regulation of immune cell migration.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23121557</pmid><doi>10.1111/bph.12042</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1188 |
| ispartof | British journal of pharmacology, 2013-03, Vol.168 (6), p.1375-1387 |
| issn | 0007-1188 1476-5381 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3596643 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Cell adhesion & migration Cells, Cultured chemokine receptors Chemokines Chemokines - metabolism Chemotaxis, Leukocyte Down-Regulation Fluorescence Resonance Energy Transfer Gene Expression Regulation HEK293 Cells heteromerization Humans Immunohistochemistry Kinetics Ligands Luminescent Proteins - genetics Luminescent Proteins - metabolism Protein Multimerization Protein Transport Receptors, CCR - genetics Receptors, CCR - metabolism Receptors, CXCR3 - genetics Receptors, CXCR3 - metabolism Recombinant Fusion Proteins - metabolism Recombinant Proteins - metabolism Research Papers RNA, Messenger T cells T-Lymphocytes - cytology T-Lymphocytes - immunology T-Lymphocytes - metabolism |
| title | Inhibition of CXCR3‐mediated chemotaxis by the human chemokine receptor‐like protein CCX‐CKR |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T23%3A34%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20CXCR3%E2%80%90mediated%20chemotaxis%20by%20the%20human%20chemokine%20receptor%E2%80%90like%20protein%20CCX%E2%80%90CKR&rft.jtitle=British%20journal%20of%20pharmacology&rft.au=Vinet,%20J&rft.date=2013-03&rft.volume=168&rft.issue=6&rft.spage=1375&rft.epage=1387&rft.pages=1375-1387&rft.issn=0007-1188&rft.eissn=1476-5381&rft_id=info:doi/10.1111/bph.12042&rft_dat=%3Cproquest_pubme%3E3315988611%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1528618632&rft_id=info:pmid/23121557&rfr_iscdi=true |