Procoagulant Soluble Tissue Factor Is Released From Endothelial Cells in Response to Inflammatory Cytokines
Inflammatory cytokines alter the hemostatic balance of endothelial cells (ECs). Alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), has recently been detected in ECs, possibly contributing to procoagulability. Agonists regulating asHTF expression and release a...
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| Veröffentlicht in: | Circulation research 2005-06, Vol.96 (12), p.1233-1239 |
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| creator | Szotowski, Björn Antoniak, Silvio Poller, Wolfgang Schultheiss, Heinz-Peter Rauch, Ursula |
| description | Inflammatory cytokines alter the hemostatic balance of endothelial cells (ECs). Alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), has recently been detected in ECs, possibly contributing to procoagulability. Agonists regulating asHTF expression and release are yet unknown. This study examines the effect of TNF-α and IL-6 on the endothelial expression of both TF variants and delineates the impact of asHTF on the procoagulability of extracellular fluids. asHTF and TF mRNA were assessed by real-time PCR, and asHTF, TF, and tissue factor pathway inhibitor (TFPI) proteins by Western blot and fluorescence microscopy before and after stimulation with TNF-α (10 ng/mL) or IL-6 (10 ng/L). The procoagulability of cell supernatant was analyzed by a chromogenic assay with or without phospholipid vesicles. We found asHTF mRNA to be maximally increased 10 minutes after TNF-α and 40 minutes after IL-6 treatment (asHTF/GAPDH ratio 0.0223±0.0069 versus 0.0012±0.0006 for control, P |
| doi_str_mv | 10.1161/01.RES.0000171805.24799.fa |
| format | Article |
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Alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), has recently been detected in ECs, possibly contributing to procoagulability. Agonists regulating asHTF expression and release are yet unknown. This study examines the effect of TNF-α and IL-6 on the endothelial expression of both TF variants and delineates the impact of asHTF on the procoagulability of extracellular fluids. asHTF and TF mRNA were assessed by real-time PCR, and asHTF, TF, and tissue factor pathway inhibitor (TFPI) proteins by Western blot and fluorescence microscopy before and after stimulation with TNF-α (10 ng/mL) or IL-6 (10 ng/L). The procoagulability of cell supernatant was analyzed by a chromogenic assay with or without phospholipid vesicles. We found asHTF mRNA to be maximally increased 10 minutes after TNF-α and 40 minutes after IL-6 treatment (asHTF/GAPDH ratio 0.0223±0.0069 versus 0.0012±0.0006 for control, P<0.001 and 0.0022±0.0004 versus 0.0012±0.0007, P<0.05, respectively). Not only was asHTF increased, but also TFPI decreased after cytokine treatment. asHTF was found in the supernatant as early as 5 hours after TNF-α stimulation, supporting factor Xa generation after relipidation (6.55±1.13 U versus 2.99±0.59 U in control supernatant, P<0.00001). Removal of asHTF from supernatants by immunoprecipitation diminished its procoagulability to baseline. The soluble TF isoform expressed and released from ECs in response to inflammatory cytokines becomes procoagulant in the presence of phospholipids. Thus, asHTF released from ECs is a marker for and a contributor to imbalanced hemostasis.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.RES.0000171805.24799.fa</identifier><identifier>PMID: 15920023</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Biological and medical sciences ; Blood Coagulation ; Cells, Cultured ; Endothelial Cells - metabolism ; Fundamental and applied biological sciences. Psychology ; Humans ; Inflammation - blood ; Interleukin-6 - pharmacology ; Lipoproteins - analysis ; Lipoproteins - physiology ; p38 Mitogen-Activated Protein Kinases - physiology ; Phospholipids - physiology ; RNA, Messenger - analysis ; Thromboplastin - biosynthesis ; Thromboplastin - genetics ; Tumor Necrosis Factor-alpha - pharmacology ; Vertebrates: cardiovascular system</subject><ispartof>Circulation research, 2005-06, Vol.96 (12), p.1233-1239</ispartof><rights>2005 American Heart Association, Inc.</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5794-37d419d261a4a437f0bf681f5accf6a538ec6a7e8f7ced86ad84ad8d516635033</citedby><cites>FETCH-LOGICAL-c5794-37d419d261a4a437f0bf681f5accf6a538ec6a7e8f7ced86ad84ad8d516635033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,3689,27931,27932</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16916135$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15920023$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Szotowski, Björn</creatorcontrib><creatorcontrib>Antoniak, Silvio</creatorcontrib><creatorcontrib>Poller, Wolfgang</creatorcontrib><creatorcontrib>Schultheiss, Heinz-Peter</creatorcontrib><creatorcontrib>Rauch, Ursula</creatorcontrib><title>Procoagulant Soluble Tissue Factor Is Released From Endothelial Cells in Response to Inflammatory Cytokines</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>Inflammatory cytokines alter the hemostatic balance of endothelial cells (ECs). Alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), has recently been detected in ECs, possibly contributing to procoagulability. Agonists regulating asHTF expression and release are yet unknown. This study examines the effect of TNF-α and IL-6 on the endothelial expression of both TF variants and delineates the impact of asHTF on the procoagulability of extracellular fluids. asHTF and TF mRNA were assessed by real-time PCR, and asHTF, TF, and tissue factor pathway inhibitor (TFPI) proteins by Western blot and fluorescence microscopy before and after stimulation with TNF-α (10 ng/mL) or IL-6 (10 ng/L). The procoagulability of cell supernatant was analyzed by a chromogenic assay with or without phospholipid vesicles. We found asHTF mRNA to be maximally increased 10 minutes after TNF-α and 40 minutes after IL-6 treatment (asHTF/GAPDH ratio 0.0223±0.0069 versus 0.0012±0.0006 for control, P<0.001 and 0.0022±0.0004 versus 0.0012±0.0007, P<0.05, respectively). Not only was asHTF increased, but also TFPI decreased after cytokine treatment. asHTF was found in the supernatant as early as 5 hours after TNF-α stimulation, supporting factor Xa generation after relipidation (6.55±1.13 U versus 2.99±0.59 U in control supernatant, P<0.00001). Removal of asHTF from supernatants by immunoprecipitation diminished its procoagulability to baseline. The soluble TF isoform expressed and released from ECs in response to inflammatory cytokines becomes procoagulant in the presence of phospholipids. Thus, asHTF released from ECs is a marker for and a contributor to imbalanced hemostasis.</description><subject>Biological and medical sciences</subject><subject>Blood Coagulation</subject><subject>Cells, Cultured</subject><subject>Endothelial Cells - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Inflammation - blood</subject><subject>Interleukin-6 - pharmacology</subject><subject>Lipoproteins - analysis</subject><subject>Lipoproteins - physiology</subject><subject>p38 Mitogen-Activated Protein Kinases - physiology</subject><subject>Phospholipids - physiology</subject><subject>RNA, Messenger - analysis</subject><subject>Thromboplastin - biosynthesis</subject><subject>Thromboplastin - genetics</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1r2zAUhs3YWLNuf2GIwXZnT7K-7N2NkKyBwkbbXYsT-WjxIluZZFPy76c2gVxWSAjE855X8BTFJ0YrxhT7Sll1t7qvaF5Ms4bKqha6bSsHr4oFk7UohdTsdbHIQFtqzulV8S6lvxkXvG7fFldMtjWlNV8U-18x2AB_Zg_jRO6Dn7ceyUOf0oxkDXYKkWwSuUOPkLAj6xgGshq7MO3Q9-DJEr1PpB8zkg5hTEimQDaj8zAMkNNHsjxOYd-PmN4Xbxz4hB_O93Xxe716WN6Utz9_bJbfb0srdStKrjvB2q5WDAQIrh3dOtUwJ8Fap0DyBq0CjY3TFrtGQdeIfDrJlOKScn5dfDnNPcTwb8Y0maFPNv8TRgxzMkq3ecuXQaa5kqxuMvjtBNoYUorozCH2A8SjYdQ8OTGUmezEXJyYZyfGQQ5_PLfM2wG7S_QsIQOfzwAkC95FGG2fLpxqcwOXmRMn7jH4CWPa-_kRo9kh-Gn3XM0pq8s8VFJVC1o-PQn-H6Pypg0</recordid><startdate>20050624</startdate><enddate>20050624</enddate><creator>Szotowski, Björn</creator><creator>Antoniak, Silvio</creator><creator>Poller, Wolfgang</creator><creator>Schultheiss, Heinz-Peter</creator><creator>Rauch, Ursula</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20050624</creationdate><title>Procoagulant Soluble Tissue Factor Is Released From Endothelial Cells in Response to Inflammatory Cytokines</title><author>Szotowski, Björn ; Antoniak, Silvio ; Poller, Wolfgang ; Schultheiss, Heinz-Peter ; Rauch, Ursula</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5794-37d419d261a4a437f0bf681f5accf6a538ec6a7e8f7ced86ad84ad8d516635033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Biological and medical sciences</topic><topic>Blood Coagulation</topic><topic>Cells, Cultured</topic><topic>Endothelial Cells - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Inflammation - blood</topic><topic>Interleukin-6 - pharmacology</topic><topic>Lipoproteins - analysis</topic><topic>Lipoproteins - physiology</topic><topic>p38 Mitogen-Activated Protein Kinases - physiology</topic><topic>Phospholipids - physiology</topic><topic>RNA, Messenger - analysis</topic><topic>Thromboplastin - biosynthesis</topic><topic>Thromboplastin - genetics</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Szotowski, Björn</creatorcontrib><creatorcontrib>Antoniak, Silvio</creatorcontrib><creatorcontrib>Poller, Wolfgang</creatorcontrib><creatorcontrib>Schultheiss, Heinz-Peter</creatorcontrib><creatorcontrib>Rauch, Ursula</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Szotowski, Björn</au><au>Antoniak, Silvio</au><au>Poller, Wolfgang</au><au>Schultheiss, Heinz-Peter</au><au>Rauch, Ursula</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Procoagulant Soluble Tissue Factor Is Released From Endothelial Cells in Response to Inflammatory Cytokines</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2005-06-24</date><risdate>2005</risdate><volume>96</volume><issue>12</issue><spage>1233</spage><epage>1239</epage><pages>1233-1239</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>Inflammatory cytokines alter the hemostatic balance of endothelial cells (ECs). Alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), has recently been detected in ECs, possibly contributing to procoagulability. Agonists regulating asHTF expression and release are yet unknown. This study examines the effect of TNF-α and IL-6 on the endothelial expression of both TF variants and delineates the impact of asHTF on the procoagulability of extracellular fluids. asHTF and TF mRNA were assessed by real-time PCR, and asHTF, TF, and tissue factor pathway inhibitor (TFPI) proteins by Western blot and fluorescence microscopy before and after stimulation with TNF-α (10 ng/mL) or IL-6 (10 ng/L). The procoagulability of cell supernatant was analyzed by a chromogenic assay with or without phospholipid vesicles. We found asHTF mRNA to be maximally increased 10 minutes after TNF-α and 40 minutes after IL-6 treatment (asHTF/GAPDH ratio 0.0223±0.0069 versus 0.0012±0.0006 for control, P<0.001 and 0.0022±0.0004 versus 0.0012±0.0007, P<0.05, respectively). Not only was asHTF increased, but also TFPI decreased after cytokine treatment. asHTF was found in the supernatant as early as 5 hours after TNF-α stimulation, supporting factor Xa generation after relipidation (6.55±1.13 U versus 2.99±0.59 U in control supernatant, P<0.00001). Removal of asHTF from supernatants by immunoprecipitation diminished its procoagulability to baseline. The soluble TF isoform expressed and released from ECs in response to inflammatory cytokines becomes procoagulant in the presence of phospholipids. Thus, asHTF released from ECs is a marker for and a contributor to imbalanced hemostasis.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>15920023</pmid><doi>10.1161/01.RES.0000171805.24799.fa</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Biological and medical sciences Blood Coagulation Cells, Cultured Endothelial Cells - metabolism Fundamental and applied biological sciences. Psychology Humans Inflammation - blood Interleukin-6 - pharmacology Lipoproteins - analysis Lipoproteins - physiology p38 Mitogen-Activated Protein Kinases - physiology Phospholipids - physiology RNA, Messenger - analysis Thromboplastin - biosynthesis Thromboplastin - genetics Tumor Necrosis Factor-alpha - pharmacology Vertebrates: cardiovascular system |
| title | Procoagulant Soluble Tissue Factor Is Released From Endothelial Cells in Response to Inflammatory Cytokines |
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