The Functional Role of the ELR Motif in CXC Chemokine-mediated Angiogenesis ()
In this study, we demonstrate that the CXC family of chemokines displays disparate angiogenic activity depending upon the presence or absence of the ELR motif. CXC chemokines containing the ELR motif (ELR-CXC chemokines) were found to be potent angiogenic factors, inducing both in vitro endothelial...
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| Veröffentlicht in: | The Journal of biological chemistry 1995-11, Vol.270 (45), p.27348-27357 |
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| container_title | The Journal of biological chemistry |
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| creator | Strieter, Robert M. Polverini, Peter J. Kunkel, Steven L. Arenberg, Douglas A. Burdick, Marie D. Kasper, James Dzuiba, Judith Van Damme, Jo Walz, Alfred Marriott, David Chan, Sham-Yuen Roczniak, Steven Shanafelt, Armen B. |
| description | In this study, we demonstrate that the CXC family of chemokines displays disparate angiogenic activity depending upon the presence or absence of the ELR motif. CXC chemokines containing the ELR motif (ELR-CXC chemokines) were found to be potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines lacking the ELR motif, platelet factor 4, interferon γ-inducible protein 10, and monokine induced by γ-interferon, not only failed to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovacularization but were found to be potent angiostatic factors in the presence of either ELR-CXC chemokines or the unrelated angiogenic factor, basic fibroblast growth factor. Additionally, mutant interleukin-8 proteins lacking the ELR motif demonstrated potent angiostatic effects in the presence of either ELR-CXC chemokines or basic fibroblast growth factor. In contrast, a mutant of monokine induced by γ-interferon containing the ELR motif was found to induce in vivo angiogenic activity. These findings suggest a functional role of the ELR motif in determining the angiogenic or angiostatic potential of CXC chemokines, supporting the hypothesis that the net biological balance between angiogenic and angiostatic CXC chemokines may play an important role in regulating overall angiogenesis. |
| doi_str_mv | 10.1074/jbc.270.45.27348 |
| format | Article |
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CXC chemokines containing the ELR motif (ELR-CXC chemokines) were found to be potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines lacking the ELR motif, platelet factor 4, interferon γ-inducible protein 10, and monokine induced by γ-interferon, not only failed to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovacularization but were found to be potent angiostatic factors in the presence of either ELR-CXC chemokines or the unrelated angiogenic factor, basic fibroblast growth factor. Additionally, mutant interleukin-8 proteins lacking the ELR motif demonstrated potent angiostatic effects in the presence of either ELR-CXC chemokines or basic fibroblast growth factor. In contrast, a mutant of monokine induced by γ-interferon containing the ELR motif was found to induce in vivo angiogenic activity. These findings suggest a functional role of the ELR motif in determining the angiogenic or angiostatic potential of CXC chemokines, supporting the hypothesis that the net biological balance between angiogenic and angiostatic CXC chemokines may play an important role in regulating overall angiogenesis.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.270.45.27348</identifier><identifier>PMID: 7592998</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Base Sequence ; Chemokines - genetics ; Chemokines - pharmacology ; Chemokines - physiology ; Cloning, Molecular ; Cornea - blood supply ; Cornea - drug effects ; DNA Primers - genetics ; Humans ; In Vitro Techniques ; Interleukin-8 - genetics ; Interleukin-8 - pharmacology ; Models, Biological ; Molecular Sequence Data ; Neovascularization, Physiologic - drug effects ; Rats</subject><ispartof>The Journal of biological chemistry, 1995-11, Vol.270 (45), p.27348-27357</ispartof><rights>1995 © 1995 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-e80e8eb0aa17f613550cc7792e2a654258988c56ea1fbb9c295ba73f151082913</citedby><cites>FETCH-LOGICAL-c562t-e80e8eb0aa17f613550cc7792e2a654258988c56ea1fbb9c295ba73f151082913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7592998$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strieter, Robert M.</creatorcontrib><creatorcontrib>Polverini, Peter J.</creatorcontrib><creatorcontrib>Kunkel, Steven L.</creatorcontrib><creatorcontrib>Arenberg, Douglas A.</creatorcontrib><creatorcontrib>Burdick, Marie D.</creatorcontrib><creatorcontrib>Kasper, James</creatorcontrib><creatorcontrib>Dzuiba, Judith</creatorcontrib><creatorcontrib>Van Damme, Jo</creatorcontrib><creatorcontrib>Walz, Alfred</creatorcontrib><creatorcontrib>Marriott, David</creatorcontrib><creatorcontrib>Chan, Sham-Yuen</creatorcontrib><creatorcontrib>Roczniak, Steven</creatorcontrib><creatorcontrib>Shanafelt, Armen B.</creatorcontrib><title>The Functional Role of the ELR Motif in CXC Chemokine-mediated Angiogenesis ()</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>In this study, we demonstrate that the CXC family of chemokines displays disparate angiogenic activity depending upon the presence or absence of the ELR motif. CXC chemokines containing the ELR motif (ELR-CXC chemokines) were found to be potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines lacking the ELR motif, platelet factor 4, interferon γ-inducible protein 10, and monokine induced by γ-interferon, not only failed to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovacularization but were found to be potent angiostatic factors in the presence of either ELR-CXC chemokines or the unrelated angiogenic factor, basic fibroblast growth factor. Additionally, mutant interleukin-8 proteins lacking the ELR motif demonstrated potent angiostatic effects in the presence of either ELR-CXC chemokines or basic fibroblast growth factor. In contrast, a mutant of monokine induced by γ-interferon containing the ELR motif was found to induce in vivo angiogenic activity. These findings suggest a functional role of the ELR motif in determining the angiogenic or angiostatic potential of CXC chemokines, supporting the hypothesis that the net biological balance between angiogenic and angiostatic CXC chemokines may play an important role in regulating overall angiogenesis.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Chemokines - genetics</subject><subject>Chemokines - pharmacology</subject><subject>Chemokines - physiology</subject><subject>Cloning, Molecular</subject><subject>Cornea - blood supply</subject><subject>Cornea - drug effects</subject><subject>DNA Primers - genetics</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Interleukin-8 - genetics</subject><subject>Interleukin-8 - pharmacology</subject><subject>Models, Biological</subject><subject>Molecular Sequence Data</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Rats</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM9LwzAUx4MoOn_cvQg5iOihM0mbpvEmxakwFcaE3UKava7RrtGmU_zvjXZ4EMRcHuR93pf3PggdUjKkRCTnT4UZMkGGCQ8lTrINNKAki6OY09kmGhDCaCQZz3bQrvdPJLxE0m20LbhkUmYDdD-tAI9Wjemsa3SNJ64G7Erche-r8QTfuc6W2DY4n-U4r2Dpnm0D0RLmVncwx5fNwroFNOCtx6dn-2ir1LWHg3XdQ4-jq2l-E40frm_zy3FkeMq6CDICGRREayrKlMacE2OEkAyYTnkSFpZZFlDQtCwKaZjkhRZxSXm4jkka76GTPvelda8r8J1aWm-grnUDbuWVEKmUnKb_glQQKhhPAkh60LTO-xZK9dLapW4_FCXqy7UKrlVwrRKuvl2HkaN19qoIQn4G1nJD_7jvV3ZRvdsWVGGdCQ5_x1z0GARhbxZa5Y2FxgTFLZhOzZ39e4dPizyW0w</recordid><startdate>19951110</startdate><enddate>19951110</enddate><creator>Strieter, Robert M.</creator><creator>Polverini, Peter J.</creator><creator>Kunkel, Steven L.</creator><creator>Arenberg, Douglas A.</creator><creator>Burdick, Marie D.</creator><creator>Kasper, James</creator><creator>Dzuiba, Judith</creator><creator>Van Damme, Jo</creator><creator>Walz, Alfred</creator><creator>Marriott, David</creator><creator>Chan, Sham-Yuen</creator><creator>Roczniak, Steven</creator><creator>Shanafelt, Armen B.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>7QR</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19951110</creationdate><title>The Functional Role of the ELR Motif in CXC Chemokine-mediated Angiogenesis ()</title><author>Strieter, Robert M. ; Polverini, Peter J. ; Kunkel, Steven L. ; Arenberg, Douglas A. ; Burdick, Marie D. ; Kasper, James ; Dzuiba, Judith ; Van Damme, Jo ; Walz, Alfred ; Marriott, David ; Chan, Sham-Yuen ; Roczniak, Steven ; Shanafelt, Armen B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-e80e8eb0aa17f613550cc7792e2a654258988c56ea1fbb9c295ba73f151082913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Chemokines - genetics</topic><topic>Chemokines - pharmacology</topic><topic>Chemokines - physiology</topic><topic>Cloning, Molecular</topic><topic>Cornea - blood supply</topic><topic>Cornea - drug effects</topic><topic>DNA Primers - genetics</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Interleukin-8 - genetics</topic><topic>Interleukin-8 - pharmacology</topic><topic>Models, Biological</topic><topic>Molecular Sequence Data</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strieter, Robert M.</creatorcontrib><creatorcontrib>Polverini, Peter J.</creatorcontrib><creatorcontrib>Kunkel, Steven L.</creatorcontrib><creatorcontrib>Arenberg, Douglas A.</creatorcontrib><creatorcontrib>Burdick, Marie D.</creatorcontrib><creatorcontrib>Kasper, James</creatorcontrib><creatorcontrib>Dzuiba, Judith</creatorcontrib><creatorcontrib>Van Damme, Jo</creatorcontrib><creatorcontrib>Walz, Alfred</creatorcontrib><creatorcontrib>Marriott, David</creatorcontrib><creatorcontrib>Chan, Sham-Yuen</creatorcontrib><creatorcontrib>Roczniak, Steven</creatorcontrib><creatorcontrib>Shanafelt, Armen B.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strieter, Robert M.</au><au>Polverini, Peter J.</au><au>Kunkel, Steven L.</au><au>Arenberg, Douglas A.</au><au>Burdick, Marie D.</au><au>Kasper, James</au><au>Dzuiba, Judith</au><au>Van Damme, Jo</au><au>Walz, Alfred</au><au>Marriott, David</au><au>Chan, Sham-Yuen</au><au>Roczniak, Steven</au><au>Shanafelt, Armen B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Functional Role of the ELR Motif in CXC Chemokine-mediated Angiogenesis ()</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1995-11-10</date><risdate>1995</risdate><volume>270</volume><issue>45</issue><spage>27348</spage><epage>27357</epage><pages>27348-27357</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>In this study, we demonstrate that the CXC family of chemokines displays disparate angiogenic activity depending upon the presence or absence of the ELR motif. CXC chemokines containing the ELR motif (ELR-CXC chemokines) were found to be potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines lacking the ELR motif, platelet factor 4, interferon γ-inducible protein 10, and monokine induced by γ-interferon, not only failed to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovacularization but were found to be potent angiostatic factors in the presence of either ELR-CXC chemokines or the unrelated angiogenic factor, basic fibroblast growth factor. Additionally, mutant interleukin-8 proteins lacking the ELR motif demonstrated potent angiostatic effects in the presence of either ELR-CXC chemokines or basic fibroblast growth factor. In contrast, a mutant of monokine induced by γ-interferon containing the ELR motif was found to induce in vivo angiogenic activity. These findings suggest a functional role of the ELR motif in determining the angiogenic or angiostatic potential of CXC chemokines, supporting the hypothesis that the net biological balance between angiogenic and angiostatic CXC chemokines may play an important role in regulating overall angiogenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>7592998</pmid><doi>10.1074/jbc.270.45.27348</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1995-11, Vol.270 (45), p.27348-27357 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Animals Base Sequence Chemokines - genetics Chemokines - pharmacology Chemokines - physiology Cloning, Molecular Cornea - blood supply Cornea - drug effects DNA Primers - genetics Humans In Vitro Techniques Interleukin-8 - genetics Interleukin-8 - pharmacology Models, Biological Molecular Sequence Data Neovascularization, Physiologic - drug effects Rats |
| title | The Functional Role of the ELR Motif in CXC Chemokine-mediated Angiogenesis () |
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