The fucosylation inhibitor, 2-fluorofucose, inhibits vaso-occlusion, leukocyte-endothelium interactions and NF-ĸB activation in transgenic sickle mice

2-Fluorofucose (2FF) blocks the fucosylation and the tethering of sialyl-Lewisx tetrasaccharide and structural variants on leukocytes and red blood cells to P- and E-selectins on activated endothelial cell surfaces. Because P- and E-selectin are required for vaso-occlusion in murine sickle cell dise...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2015-02, Vol.10 (2), p.e0117772-e0117772
Hauptverfasser: Belcher, John D, Chen, Chunsheng, Nguyen, Julia, Abdulla, Fuad, Nguyen, Phong, Nguyen, Minh, Okeley, Nicole M, Benjamin, Dennis R, Senter, Peter D, Vercellotti, Gregory M
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page e0117772
container_issue 2
container_start_page e0117772
container_title PloS one
container_volume 10
creator Belcher, John D
Chen, Chunsheng
Nguyen, Julia
Abdulla, Fuad
Nguyen, Phong
Nguyen, Minh
Okeley, Nicole M
Benjamin, Dennis R
Senter, Peter D
Vercellotti, Gregory M
description 2-Fluorofucose (2FF) blocks the fucosylation and the tethering of sialyl-Lewisx tetrasaccharide and structural variants on leukocytes and red blood cells to P- and E-selectins on activated endothelial cell surfaces. Because P- and E-selectin are required for vaso-occlusion in murine sickle cell disease (SCD), we investigated whether 2FF would inhibit vaso-occlusion in SCD mice. Microvascular stasis was measured in subcutaneous venules in NY1DD and HbSS-Townes SCD mice with dorsal skin-fold chambers after infusion of hemoglobin or exposure to hypoxia/reoxygenation. 2FF in drinking water or administered by gavage inhibited stasis in sickle mice in a dose-responsive manner. Significant inhibitory effects on stasis were seen 1 day post-treatment. 2FF treatment of SCD mice also significantly reduced leukocyte rolling and adhesion along the vessel walls of SCD mice and the static adhesion of neutrophils and sickle red blood cells isolated from 2FF-treated SCD mice to resting and activated endothelial cells. Total white blood cell counts increased in response to 2FF. NF-ĸB activation and VCAM-1 and E-selectin expression were inhibited in the livers of SCD mice consistent with an overall decrease in vascular inflammation and ischemia-reperfusion physiology. Pretreatment with 2FF completely eliminated heme-induced lethality in HbSS-Townes mice, consistent with the observed anti-inflammatory and anti-adhesive properties of 2FF in SCD mice. These data suggest that 2FF may be beneficial for preventing or treating vaso-occlusive crises in SCD patients.
doi_str_mv 10.1371/journal.pone.0117772
format Article
fullrecord <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1658065692</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_1b125e000e0f4fb68d53ed4881a03d4d</doaj_id><sourcerecordid>1658422066</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4372-31b547e6838d9aa1fa6db6b35a0573b535a6b8edfbdbd045250274b83ec111b73</originalsourceid><addsrcrecordid>eNptUs1uEzEQXiEQLYU3QGCJC4ds8M_au7lUgopCpQou5Wz5ZzZx6rWDvRspT8Kr8AA8GJtmU7WIk0fz_cyM9RXFa4LnhNXkwzoOKSg_38QAc0xIXdf0SXFKFoyWgmL29EF9UrzIeY0xZ40Qz4sTymssCGlOi183K0DtYGLeedW7GJALK6ddH9MM0bL1Q0zxDofZEcpoq3IsozF-yKNkhjwMt9Hseigh2NivwLuhG-k9JGX2rhmpYNG3y_LP709o39oeh6E-qZCXEJxB2ZlbD6hzBl4Wz1rlM7ya3rPix-Xnm4uv5fX3L1cXH69LU7GaloxoXtUgGtbYhVKkVcJqoRlXmNdM87EQugHbaqstrjjlmNaVbhgYQoiu2Vnx9uC78THL6U-zJII3WHCxoCPj6sCwUa3lJrlOpZ2Mysm7RkxLqVLvjAdJNKEcMMaA26rVorGcga2ahijMbGVHr_Np2qA7sAbCeL1_ZPoYCW4ll3ErK8bGfdho8H4ySPHnALmXncsGvFcB4nDYu6IUCzFS3_1D_f911YFlUsw5QXu_DMFyn7OjSu5zJqecjbI3Dw-5Fx2Dxf4C-tvVCQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1658065692</pqid></control><display><type>article</type><title>The fucosylation inhibitor, 2-fluorofucose, inhibits vaso-occlusion, leukocyte-endothelium interactions and NF-ĸB activation in transgenic sickle mice</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Belcher, John D ; Chen, Chunsheng ; Nguyen, Julia ; Abdulla, Fuad ; Nguyen, Phong ; Nguyen, Minh ; Okeley, Nicole M ; Benjamin, Dennis R ; Senter, Peter D ; Vercellotti, Gregory M</creator><contributor>Sperandio, Markus</contributor><creatorcontrib>Belcher, John D ; Chen, Chunsheng ; Nguyen, Julia ; Abdulla, Fuad ; Nguyen, Phong ; Nguyen, Minh ; Okeley, Nicole M ; Benjamin, Dennis R ; Senter, Peter D ; Vercellotti, Gregory M ; Sperandio, Markus</creatorcontrib><description>2-Fluorofucose (2FF) blocks the fucosylation and the tethering of sialyl-Lewisx tetrasaccharide and structural variants on leukocytes and red blood cells to P- and E-selectins on activated endothelial cell surfaces. Because P- and E-selectin are required for vaso-occlusion in murine sickle cell disease (SCD), we investigated whether 2FF would inhibit vaso-occlusion in SCD mice. Microvascular stasis was measured in subcutaneous venules in NY1DD and HbSS-Townes SCD mice with dorsal skin-fold chambers after infusion of hemoglobin or exposure to hypoxia/reoxygenation. 2FF in drinking water or administered by gavage inhibited stasis in sickle mice in a dose-responsive manner. Significant inhibitory effects on stasis were seen 1 day post-treatment. 2FF treatment of SCD mice also significantly reduced leukocyte rolling and adhesion along the vessel walls of SCD mice and the static adhesion of neutrophils and sickle red blood cells isolated from 2FF-treated SCD mice to resting and activated endothelial cells. Total white blood cell counts increased in response to 2FF. NF-ĸB activation and VCAM-1 and E-selectin expression were inhibited in the livers of SCD mice consistent with an overall decrease in vascular inflammation and ischemia-reperfusion physiology. Pretreatment with 2FF completely eliminated heme-induced lethality in HbSS-Townes mice, consistent with the observed anti-inflammatory and anti-adhesive properties of 2FF in SCD mice. These data suggest that 2FF may be beneficial for preventing or treating vaso-occlusive crises in SCD patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0117772</identifier><identifier>PMID: 25706118</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adhesion ; Anemia ; Anemia, Sickle Cell - drug therapy ; Anemia, Sickle Cell - metabolism ; Animals ; Biology ; Blood ; Blood cells ; Cell activation ; Cell Adhesion - drug effects ; Cells, Cultured ; Disease Models, Animal ; Drinking water ; E-selectin ; Endothelial cells ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Endothelium ; Endothelium - drug effects ; Endothelium - metabolism ; Erythrocytes ; Erythrocytes - drug effects ; Erythrocytes - metabolism ; Female ; Fucose - pharmacology ; Genetics ; Hair ; Hematology ; Heme ; Heme - metabolism ; Hemoglobin ; Hemoglobins - metabolism ; Humans ; Hypoxia ; Inflammation ; Inflammation - drug therapy ; Inflammation - metabolism ; Infusion ; Inhibition ; Ischemia ; Lethality ; Leukocyte rolling ; Leukocyte Rolling - drug effects ; Leukocytes ; Leukocytes (neutrophilic) ; Leukocytes - drug effects ; Leukocytes - metabolism ; Ligands ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microcirculation - drug effects ; Microscopy ; Microvasculature ; Neutrophils ; Neutrophils - drug effects ; Neutrophils - metabolism ; NF-kappa B - metabolism ; Occlusion ; Oncology ; Pretreatment ; Red blood cells ; Reperfusion ; Rodents ; Selectins ; Sickle cell disease ; Skin ; Tethering ; Transgenic mice ; Vascular cell adhesion molecule 1 ; Vascular Cell Adhesion Molecule-1 - metabolism ; Venules - drug effects ; Venules - metabolism ; White blood cells</subject><ispartof>PloS one, 2015-02, Vol.10 (2), p.e0117772-e0117772</ispartof><rights>2015 Belcher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Belcher et al 2015 Belcher et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4372-31b547e6838d9aa1fa6db6b35a0573b535a6b8edfbdbd045250274b83ec111b73</citedby><cites>FETCH-LOGICAL-c4372-31b547e6838d9aa1fa6db6b35a0573b535a6b8edfbdbd045250274b83ec111b73</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/PMC4338063/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338063/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25706118$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Sperandio, Markus</contributor><creatorcontrib>Belcher, John D</creatorcontrib><creatorcontrib>Chen, Chunsheng</creatorcontrib><creatorcontrib>Nguyen, Julia</creatorcontrib><creatorcontrib>Abdulla, Fuad</creatorcontrib><creatorcontrib>Nguyen, Phong</creatorcontrib><creatorcontrib>Nguyen, Minh</creatorcontrib><creatorcontrib>Okeley, Nicole M</creatorcontrib><creatorcontrib>Benjamin, Dennis R</creatorcontrib><creatorcontrib>Senter, Peter D</creatorcontrib><creatorcontrib>Vercellotti, Gregory M</creatorcontrib><title>The fucosylation inhibitor, 2-fluorofucose, inhibits vaso-occlusion, leukocyte-endothelium interactions and NF-ĸB activation in transgenic sickle mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>2-Fluorofucose (2FF) blocks the fucosylation and the tethering of sialyl-Lewisx tetrasaccharide and structural variants on leukocytes and red blood cells to P- and E-selectins on activated endothelial cell surfaces. Because P- and E-selectin are required for vaso-occlusion in murine sickle cell disease (SCD), we investigated whether 2FF would inhibit vaso-occlusion in SCD mice. Microvascular stasis was measured in subcutaneous venules in NY1DD and HbSS-Townes SCD mice with dorsal skin-fold chambers after infusion of hemoglobin or exposure to hypoxia/reoxygenation. 2FF in drinking water or administered by gavage inhibited stasis in sickle mice in a dose-responsive manner. Significant inhibitory effects on stasis were seen 1 day post-treatment. 2FF treatment of SCD mice also significantly reduced leukocyte rolling and adhesion along the vessel walls of SCD mice and the static adhesion of neutrophils and sickle red blood cells isolated from 2FF-treated SCD mice to resting and activated endothelial cells. Total white blood cell counts increased in response to 2FF. NF-ĸB activation and VCAM-1 and E-selectin expression were inhibited in the livers of SCD mice consistent with an overall decrease in vascular inflammation and ischemia-reperfusion physiology. Pretreatment with 2FF completely eliminated heme-induced lethality in HbSS-Townes mice, consistent with the observed anti-inflammatory and anti-adhesive properties of 2FF in SCD mice. These data suggest that 2FF may be beneficial for preventing or treating vaso-occlusive crises in SCD patients.</description><subject>Adhesion</subject><subject>Anemia</subject><subject>Anemia, Sickle Cell - drug therapy</subject><subject>Anemia, Sickle Cell - metabolism</subject><subject>Animals</subject><subject>Biology</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Cell activation</subject><subject>Cell Adhesion - drug effects</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>Drinking water</subject><subject>E-selectin</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>Endothelium - drug effects</subject><subject>Endothelium - metabolism</subject><subject>Erythrocytes</subject><subject>Erythrocytes - drug effects</subject><subject>Erythrocytes - metabolism</subject><subject>Female</subject><subject>Fucose - pharmacology</subject><subject>Genetics</subject><subject>Hair</subject><subject>Hematology</subject><subject>Heme</subject><subject>Heme - metabolism</subject><subject>Hemoglobin</subject><subject>Hemoglobins - metabolism</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - metabolism</subject><subject>Infusion</subject><subject>Inhibition</subject><subject>Ischemia</subject><subject>Lethality</subject><subject>Leukocyte rolling</subject><subject>Leukocyte Rolling - drug effects</subject><subject>Leukocytes</subject><subject>Leukocytes (neutrophilic)</subject><subject>Leukocytes - drug effects</subject><subject>Leukocytes - metabolism</subject><subject>Ligands</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microcirculation - drug effects</subject><subject>Microscopy</subject><subject>Microvasculature</subject><subject>Neutrophils</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Occlusion</subject><subject>Oncology</subject><subject>Pretreatment</subject><subject>Red blood cells</subject><subject>Reperfusion</subject><subject>Rodents</subject><subject>Selectins</subject><subject>Sickle cell disease</subject><subject>Skin</subject><subject>Tethering</subject><subject>Transgenic mice</subject><subject>Vascular cell adhesion molecule 1</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><subject>Venules - drug effects</subject><subject>Venules - metabolism</subject><subject>White blood cells</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUs1uEzEQXiEQLYU3QGCJC4ds8M_au7lUgopCpQou5Wz5ZzZx6rWDvRspT8Kr8AA8GJtmU7WIk0fz_cyM9RXFa4LnhNXkwzoOKSg_38QAc0xIXdf0SXFKFoyWgmL29EF9UrzIeY0xZ40Qz4sTymssCGlOi183K0DtYGLeedW7GJALK6ddH9MM0bL1Q0zxDofZEcpoq3IsozF-yKNkhjwMt9Hseigh2NivwLuhG-k9JGX2rhmpYNG3y_LP709o39oeh6E-qZCXEJxB2ZlbD6hzBl4Wz1rlM7ya3rPix-Xnm4uv5fX3L1cXH69LU7GaloxoXtUgGtbYhVKkVcJqoRlXmNdM87EQugHbaqstrjjlmNaVbhgYQoiu2Vnx9uC78THL6U-zJII3WHCxoCPj6sCwUa3lJrlOpZ2Mysm7RkxLqVLvjAdJNKEcMMaA26rVorGcga2ahijMbGVHr_Np2qA7sAbCeL1_ZPoYCW4ll3ErK8bGfdho8H4ySPHnALmXncsGvFcB4nDYu6IUCzFS3_1D_f911YFlUsw5QXu_DMFyn7OjSu5zJqecjbI3Dw-5Fx2Dxf4C-tvVCQ</recordid><startdate>20150223</startdate><enddate>20150223</enddate><creator>Belcher, John D</creator><creator>Chen, Chunsheng</creator><creator>Nguyen, Julia</creator><creator>Abdulla, Fuad</creator><creator>Nguyen, Phong</creator><creator>Nguyen, Minh</creator><creator>Okeley, Nicole M</creator><creator>Benjamin, Dennis R</creator><creator>Senter, Peter D</creator><creator>Vercellotti, Gregory M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150223</creationdate><title>The fucosylation inhibitor, 2-fluorofucose, inhibits vaso-occlusion, leukocyte-endothelium interactions and NF-ĸB activation in transgenic sickle mice</title><author>Belcher, John D ; Chen, Chunsheng ; Nguyen, Julia ; Abdulla, Fuad ; Nguyen, Phong ; Nguyen, Minh ; Okeley, Nicole M ; Benjamin, Dennis R ; Senter, Peter D ; Vercellotti, Gregory M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4372-31b547e6838d9aa1fa6db6b35a0573b535a6b8edfbdbd045250274b83ec111b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adhesion</topic><topic>Anemia</topic><topic>Anemia, Sickle Cell - drug therapy</topic><topic>Anemia, Sickle Cell - metabolism</topic><topic>Animals</topic><topic>Biology</topic><topic>Blood</topic><topic>Blood cells</topic><topic>Cell activation</topic><topic>Cell Adhesion - drug effects</topic><topic>Cells, Cultured</topic><topic>Disease Models, Animal</topic><topic>Drinking water</topic><topic>E-selectin</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium</topic><topic>Endothelium - drug effects</topic><topic>Endothelium - metabolism</topic><topic>Erythrocytes</topic><topic>Erythrocytes - drug effects</topic><topic>Erythrocytes - metabolism</topic><topic>Female</topic><topic>Fucose - pharmacology</topic><topic>Genetics</topic><topic>Hair</topic><topic>Hematology</topic><topic>Heme</topic><topic>Heme - metabolism</topic><topic>Hemoglobin</topic><topic>Hemoglobins - metabolism</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - metabolism</topic><topic>Infusion</topic><topic>Inhibition</topic><topic>Ischemia</topic><topic>Lethality</topic><topic>Leukocyte rolling</topic><topic>Leukocyte Rolling - drug effects</topic><topic>Leukocytes</topic><topic>Leukocytes (neutrophilic)</topic><topic>Leukocytes - drug effects</topic><topic>Leukocytes - metabolism</topic><topic>Ligands</topic><topic>Male</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microcirculation - drug effects</topic><topic>Microscopy</topic><topic>Microvasculature</topic><topic>Neutrophils</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>Occlusion</topic><topic>Oncology</topic><topic>Pretreatment</topic><topic>Red blood cells</topic><topic>Reperfusion</topic><topic>Rodents</topic><topic>Selectins</topic><topic>Sickle cell disease</topic><topic>Skin</topic><topic>Tethering</topic><topic>Transgenic mice</topic><topic>Vascular cell adhesion molecule 1</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><topic>Venules - drug effects</topic><topic>Venules - metabolism</topic><topic>White blood cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Belcher, John D</creatorcontrib><creatorcontrib>Chen, Chunsheng</creatorcontrib><creatorcontrib>Nguyen, Julia</creatorcontrib><creatorcontrib>Abdulla, Fuad</creatorcontrib><creatorcontrib>Nguyen, Phong</creatorcontrib><creatorcontrib>Nguyen, Minh</creatorcontrib><creatorcontrib>Okeley, Nicole M</creatorcontrib><creatorcontrib>Benjamin, Dennis R</creatorcontrib><creatorcontrib>Senter, Peter D</creatorcontrib><creatorcontrib>Vercellotti, Gregory M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing &amp; Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Belcher, John D</au><au>Chen, Chunsheng</au><au>Nguyen, Julia</au><au>Abdulla, Fuad</au><au>Nguyen, Phong</au><au>Nguyen, Minh</au><au>Okeley, Nicole M</au><au>Benjamin, Dennis R</au><au>Senter, Peter D</au><au>Vercellotti, Gregory M</au><au>Sperandio, Markus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The fucosylation inhibitor, 2-fluorofucose, inhibits vaso-occlusion, leukocyte-endothelium interactions and NF-ĸB activation in transgenic sickle mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-02-23</date><risdate>2015</risdate><volume>10</volume><issue>2</issue><spage>e0117772</spage><epage>e0117772</epage><pages>e0117772-e0117772</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>2-Fluorofucose (2FF) blocks the fucosylation and the tethering of sialyl-Lewisx tetrasaccharide and structural variants on leukocytes and red blood cells to P- and E-selectins on activated endothelial cell surfaces. Because P- and E-selectin are required for vaso-occlusion in murine sickle cell disease (SCD), we investigated whether 2FF would inhibit vaso-occlusion in SCD mice. Microvascular stasis was measured in subcutaneous venules in NY1DD and HbSS-Townes SCD mice with dorsal skin-fold chambers after infusion of hemoglobin or exposure to hypoxia/reoxygenation. 2FF in drinking water or administered by gavage inhibited stasis in sickle mice in a dose-responsive manner. Significant inhibitory effects on stasis were seen 1 day post-treatment. 2FF treatment of SCD mice also significantly reduced leukocyte rolling and adhesion along the vessel walls of SCD mice and the static adhesion of neutrophils and sickle red blood cells isolated from 2FF-treated SCD mice to resting and activated endothelial cells. Total white blood cell counts increased in response to 2FF. NF-ĸB activation and VCAM-1 and E-selectin expression were inhibited in the livers of SCD mice consistent with an overall decrease in vascular inflammation and ischemia-reperfusion physiology. Pretreatment with 2FF completely eliminated heme-induced lethality in HbSS-Townes mice, consistent with the observed anti-inflammatory and anti-adhesive properties of 2FF in SCD mice. These data suggest that 2FF may be beneficial for preventing or treating vaso-occlusive crises in SCD patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25706118</pmid><doi>10.1371/journal.pone.0117772</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2015-02, Vol.10 (2), p.e0117772-e0117772
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1658065692
source MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry
subjects Adhesion
Anemia
Anemia, Sickle Cell - drug therapy
Anemia, Sickle Cell - metabolism
Animals
Biology
Blood
Blood cells
Cell activation
Cell Adhesion - drug effects
Cells, Cultured
Disease Models, Animal
Drinking water
E-selectin
Endothelial cells
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Endothelium
Endothelium - drug effects
Endothelium - metabolism
Erythrocytes
Erythrocytes - drug effects
Erythrocytes - metabolism
Female
Fucose - pharmacology
Genetics
Hair
Hematology
Heme
Heme - metabolism
Hemoglobin
Hemoglobins - metabolism
Humans
Hypoxia
Inflammation
Inflammation - drug therapy
Inflammation - metabolism
Infusion
Inhibition
Ischemia
Lethality
Leukocyte rolling
Leukocyte Rolling - drug effects
Leukocytes
Leukocytes (neutrophilic)
Leukocytes - drug effects
Leukocytes - metabolism
Ligands
Male
Medicine
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microcirculation - drug effects
Microscopy
Microvasculature
Neutrophils
Neutrophils - drug effects
Neutrophils - metabolism
NF-kappa B - metabolism
Occlusion
Oncology
Pretreatment
Red blood cells
Reperfusion
Rodents
Selectins
Sickle cell disease
Skin
Tethering
Transgenic mice
Vascular cell adhesion molecule 1
Vascular Cell Adhesion Molecule-1 - metabolism
Venules - drug effects
Venules - metabolism
White blood cells
title The fucosylation inhibitor, 2-fluorofucose, inhibits vaso-occlusion, leukocyte-endothelium interactions and NF-ĸB activation in transgenic sickle mice
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T00%3A42%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20fucosylation%20inhibitor,%202-fluorofucose,%20inhibits%20vaso-occlusion,%20leukocyte-endothelium%20interactions%20and%20NF-%C4%B8B%20activation%20in%20transgenic%20sickle%20mice&rft.jtitle=PloS%20one&rft.au=Belcher,%20John%20D&rft.date=2015-02-23&rft.volume=10&rft.issue=2&rft.spage=e0117772&rft.epage=e0117772&rft.pages=e0117772-e0117772&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0117772&rft_dat=%3Cproquest_plos_%3E1658422066%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1658065692&rft_id=info:pmid/25706118&rft_doaj_id=oai_doaj_org_article_1b125e000e0f4fb68d53ed4881a03d4d&rfr_iscdi=true