The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo
Selectins and their ligands support leuocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC‐1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P‐, E‐, and L‐selectin in vitro, has anti‐inflammatory effects in vivo, and...
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| Veröffentlicht in: | Journal of leukocyte biology 2005-01, Vol.77 (1), p.59-66 |
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| container_title | Journal of leukocyte biology |
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| creator | Hicks, Anne E. R. Abbitt, Kate B. Dodd, Paul Ridger, Victoria C. Hellewell, Paul G. Norman, Keith E. |
| description | Selectins and their ligands support leuocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC‐1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P‐, E‐, and L‐selectin in vitro, has anti‐inflammatory effects in vivo, and recently underwent phase II clinical trials for childhood asthma and psoriasis. We studied whether the anti‐inflammatory effects of TBC‐1269 could be related to leukocyte rolling in vivo. Although TBC‐1269 inhibited rolling of a murine leukocyte cell line on murine P‐selectin in vitro and thioglycollate‐induced peritonitis in vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC‐1269 reduced neutrophil recruitment in thioglycollate‐induced peritonitis in wild‐type and P‐selectin−/− mice but not in E‐selectin−/− mice. We suggest that the in vivo effects of TBC‐1269 may be mediated through E‐selectin but do not appear to involve leukocyte rolling. |
| doi_str_mv | 10.1189/jlb.1103573 |
| format | Article |
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R. ; Abbitt, Kate B. ; Dodd, Paul ; Ridger, Victoria C. ; Hellewell, Paul G. ; Norman, Keith E.</creator><creatorcontrib>Hicks, Anne E. R. ; Abbitt, Kate B. ; Dodd, Paul ; Ridger, Victoria C. ; Hellewell, Paul G. ; Norman, Keith E.</creatorcontrib><description>Selectins and their ligands support leuocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC‐1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P‐, E‐, and L‐selectin in vitro, has anti‐inflammatory effects in vivo, and recently underwent phase II clinical trials for childhood asthma and psoriasis. We studied whether the anti‐inflammatory effects of TBC‐1269 could be related to leukocyte rolling in vivo. Although TBC‐1269 inhibited rolling of a murine leukocyte cell line on murine P‐selectin in vitro and thioglycollate‐induced peritonitis in vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC‐1269 reduced neutrophil recruitment in thioglycollate‐induced peritonitis in wild‐type and P‐selectin−/− mice but not in E‐selectin−/− mice. We suggest that the in vivo effects of TBC‐1269 may be mediated through E‐selectin but do not appear to involve leukocyte rolling.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.1103573</identifier><identifier>PMID: 15466915</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>Animals ; Binding, Competitive ; Biphenyl Compounds - therapeutic use ; E-Selectin - genetics ; E-Selectin - immunology ; E-Selectin - physiology ; flow‐based adhesion assay ; in vivo animal models ; inflammation ; Inflammation - pathology ; intravital microscopy ; Leukocytes - immunology ; Leukocytes - metabolism ; Leukocytes - pathology ; Ligands ; Male ; Mannose - analogs & derivatives ; Mannosides - therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Mimicry ; neutrophils ; Neutrophils - immunology ; Neutrophils - metabolism ; Neutrophils - pathology ; P-Selectin - genetics ; P-Selectin - immunology ; P-Selectin - physiology ; Peptoids - chemistry ; Peptoids - pharmacology ; Peritonitis - chemically induced ; Peritonitis - pathology ; sialyl LewisX ; Thioglycolates - toxicity ; venules ; Venules - cytology</subject><ispartof>Journal of leukocyte biology, 2005-01, Vol.77 (1), p.59-66</ispartof><rights>2005 Society for Leukocyte Biology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3949-9521e242386c5e9c99b39781552d3df6f10a66057fafc3deefda41e72cb5440a3</citedby><cites>FETCH-LOGICAL-c3949-9521e242386c5e9c99b39781552d3df6f10a66057fafc3deefda41e72cb5440a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.1103573$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.1103573$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27915,27916,45565,45566</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15466915$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hicks, Anne E. R.</creatorcontrib><creatorcontrib>Abbitt, Kate B.</creatorcontrib><creatorcontrib>Dodd, Paul</creatorcontrib><creatorcontrib>Ridger, Victoria C.</creatorcontrib><creatorcontrib>Hellewell, Paul G.</creatorcontrib><creatorcontrib>Norman, Keith E.</creatorcontrib><title>The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>Selectins and their ligands support leuocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC‐1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P‐, E‐, and L‐selectin in vitro, has anti‐inflammatory effects in vivo, and recently underwent phase II clinical trials for childhood asthma and psoriasis. We studied whether the anti‐inflammatory effects of TBC‐1269 could be related to leukocyte rolling in vivo. Although TBC‐1269 inhibited rolling of a murine leukocyte cell line on murine P‐selectin in vitro and thioglycollate‐induced peritonitis in vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC‐1269 reduced neutrophil recruitment in thioglycollate‐induced peritonitis in wild‐type and P‐selectin−/− mice but not in E‐selectin−/− mice. We suggest that the in vivo effects of TBC‐1269 may be mediated through E‐selectin but do not appear to involve leukocyte rolling.</description><subject>Animals</subject><subject>Binding, Competitive</subject><subject>Biphenyl Compounds - therapeutic use</subject><subject>E-Selectin - genetics</subject><subject>E-Selectin - immunology</subject><subject>E-Selectin - physiology</subject><subject>flow‐based adhesion assay</subject><subject>in vivo animal models</subject><subject>inflammation</subject><subject>Inflammation - pathology</subject><subject>intravital microscopy</subject><subject>Leukocytes - immunology</subject><subject>Leukocytes - metabolism</subject><subject>Leukocytes - pathology</subject><subject>Ligands</subject><subject>Male</subject><subject>Mannose - analogs & derivatives</subject><subject>Mannosides - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Molecular Mimicry</subject><subject>neutrophils</subject><subject>Neutrophils - immunology</subject><subject>Neutrophils - metabolism</subject><subject>Neutrophils - pathology</subject><subject>P-Selectin - genetics</subject><subject>P-Selectin - immunology</subject><subject>P-Selectin - physiology</subject><subject>Peptoids - chemistry</subject><subject>Peptoids - pharmacology</subject><subject>Peritonitis - chemically induced</subject><subject>Peritonitis - pathology</subject><subject>sialyl LewisX</subject><subject>Thioglycolates - toxicity</subject><subject>venules</subject><subject>Venules - cytology</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD9v2zAQxYmgReI6mbIXHLrFaklRpMwxNpL-gYEuzkxQ1NGmS4kGKVvwh-h3Lg0byNbp3uH93h3wEHqk5Culc_lt55ssCOM1u0ETKtm8YKJmH9CE1BUteEXIHfqU0o4QwkpBbtEd5ZUQkvIJ-rveAtb94ArXW6-7Tg8hnjBYC2ZIOFiscQKfF9dj7za6b3HnOhicmeH1YlnQUsgZ1hFwH4YMR0gHP5yDJnT7zA3uCNj1W9dkGfqz4-HwJ5jTADgG712_yT4-umO4Rx-t9gkernOK3l5f1ssfxer395_L51VhmKxkIXlJoaxKNheGgzRSNkzWc8p52bLWCkuJFoLw2mprWAtgW11RqEvT8Koimk3R0-WuiSGlCFbto-t0PClK1LlUlUtV11Iz_flC7w9NB-07e20xA-QCjM7D6X-31K_VghAuc-TLJbJ1m-3oIqjUae_zh1KN41jXiqqM_QMMAY83</recordid><startdate>200501</startdate><enddate>200501</enddate><creator>Hicks, Anne E. 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R. ; Abbitt, Kate B. ; Dodd, Paul ; Ridger, Victoria C. ; Hellewell, Paul G. ; Norman, Keith E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3949-9521e242386c5e9c99b39781552d3df6f10a66057fafc3deefda41e72cb5440a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Binding, Competitive</topic><topic>Biphenyl Compounds - therapeutic use</topic><topic>E-Selectin - genetics</topic><topic>E-Selectin - immunology</topic><topic>E-Selectin - physiology</topic><topic>flow‐based adhesion assay</topic><topic>in vivo animal models</topic><topic>inflammation</topic><topic>Inflammation - pathology</topic><topic>intravital microscopy</topic><topic>Leukocytes - immunology</topic><topic>Leukocytes - metabolism</topic><topic>Leukocytes - pathology</topic><topic>Ligands</topic><topic>Male</topic><topic>Mannose - analogs & derivatives</topic><topic>Mannosides - therapeutic use</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Molecular Mimicry</topic><topic>neutrophils</topic><topic>Neutrophils - immunology</topic><topic>Neutrophils - metabolism</topic><topic>Neutrophils - pathology</topic><topic>P-Selectin - genetics</topic><topic>P-Selectin - immunology</topic><topic>P-Selectin - physiology</topic><topic>Peptoids - chemistry</topic><topic>Peptoids - pharmacology</topic><topic>Peritonitis - chemically induced</topic><topic>Peritonitis - pathology</topic><topic>sialyl LewisX</topic><topic>Thioglycolates - toxicity</topic><topic>venules</topic><topic>Venules - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hicks, Anne E. R.</creatorcontrib><creatorcontrib>Abbitt, Kate B.</creatorcontrib><creatorcontrib>Dodd, Paul</creatorcontrib><creatorcontrib>Ridger, Victoria C.</creatorcontrib><creatorcontrib>Hellewell, Paul G.</creatorcontrib><creatorcontrib>Norman, Keith E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hicks, Anne E. R.</au><au>Abbitt, Kate B.</au><au>Dodd, Paul</au><au>Ridger, Victoria C.</au><au>Hellewell, Paul G.</au><au>Norman, Keith E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2005-01</date><risdate>2005</risdate><volume>77</volume><issue>1</issue><spage>59</spage><epage>66</epage><pages>59-66</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>Selectins and their ligands support leuocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC‐1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P‐, E‐, and L‐selectin in vitro, has anti‐inflammatory effects in vivo, and recently underwent phase II clinical trials for childhood asthma and psoriasis. We studied whether the anti‐inflammatory effects of TBC‐1269 could be related to leukocyte rolling in vivo. Although TBC‐1269 inhibited rolling of a murine leukocyte cell line on murine P‐selectin in vitro and thioglycollate‐induced peritonitis in vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC‐1269 reduced neutrophil recruitment in thioglycollate‐induced peritonitis in wild‐type and P‐selectin−/− mice but not in E‐selectin−/− mice. 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| ispartof | Journal of leukocyte biology, 2005-01, Vol.77 (1), p.59-66 |
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| source | Wiley-Blackwell Journals; MEDLINE; Oxford Journals Online; EZB Electronic Journals Library |
| subjects | Animals Binding, Competitive Biphenyl Compounds - therapeutic use E-Selectin - genetics E-Selectin - immunology E-Selectin - physiology flow‐based adhesion assay in vivo animal models inflammation Inflammation - pathology intravital microscopy Leukocytes - immunology Leukocytes - metabolism Leukocytes - pathology Ligands Male Mannose - analogs & derivatives Mannosides - therapeutic use Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Molecular Mimicry neutrophils Neutrophils - immunology Neutrophils - metabolism Neutrophils - pathology P-Selectin - genetics P-Selectin - immunology P-Selectin - physiology Peptoids - chemistry Peptoids - pharmacology Peritonitis - chemically induced Peritonitis - pathology sialyl LewisX Thioglycolates - toxicity venules Venules - cytology |
| title | The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo |
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