High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats
Objective High mobility group box 1 (HMGB1) is an important factor in the development of sepsis. Previous work suggests that antithrombin III (ATIII) inhibits inflammation, but the mechanism of action is still poorly understood. Design and setting Prospective controlled animal study in a university...
Gespeichert in:
| Veröffentlicht in: | Intensive care medicine 2008-02, Vol.34 (2), p.361-367 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 367 |
|---|---|
| container_issue | 2 |
| container_start_page | 361 |
| container_title | Intensive care medicine |
| container_volume | 34 |
| creator | Hagiwara, Satoshi Iwasaka, Hideo Matsumoto, Shigekiyo Noguchi, Takayuki |
| description | Objective
High mobility group box 1 (HMGB1) is an important factor in the development of sepsis. Previous work suggests that antithrombin III (ATIII) inhibits inflammation, but the mechanism of action is still poorly understood.
Design and setting
Prospective controlled animal study in a university laboratory.
Materials
Rats were randomly divided into a lipopolysaccharide (LPS)-induced sepsis control group and an ATIII-treated experimental group. Animals in the experimental group received a bolus of 250 units/kg of ATIII injected into the tail vein.
Measurements and results
Animals receiving high-dose ATIII (250 units/kg) had significantly improved lung histopathology and survival compared to the control rats. We measured serum and lung levels of various cytokines and HMGB1 at regular intervals from 0 to 12 h after the induction of sepsis and demonstrated lower HMGB1 levels over time in ATIII-treated animals. In an in vitro experiment, we stimulated the mouse macrophage cell line RAW 264.7 with LPS in the presence or absence of ATIII. Subsequent measurement of HMGB1 concentrations in the supernatant and cell signaling molecules in cell lysates revealed an ATIII dose-dependent decrease in HMGB1 release. Furthermore, inhibition of IkB and p42 phosphorylation was observed with the administration of ATIII, suggestive of downstream signaling pathways.
Conclusions
High-dose ATIII decreases lung pathology and reduces mortality in a rat sepsis model. This finding may be mediated by the inhibition of HMGB1. |
| doi_str_mv | 10.1007/s00134-007-0887-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70267521</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1432002771</sourcerecordid><originalsourceid>FETCH-LOGICAL-c465t-3a0cf5963d985f71ed7c119c5f555f06b572dd8bd0814a87eee956beb3e30bfc3</originalsourceid><addsrcrecordid>eNp1kN1rFDEUxYModq3-Ab5IEOxb2nwn82iLdhcqfdHnkK_ZzTKTqclMsf99s-xiQfDpHri_c-_hAPCR4EuCsbqqGBPGUZMIa62QeAVWhDOKCGX6NVhhxiniktMz8K7WfaOVFOQtOCOq41hxvQJunbY7GKYaoc1zmndlGl3KcLPZwJR3yaW5wvWP22vS9gGm8aFMj7HCmMM0T39SRimHxccArV_mCIclb5txv5SnNmCxc30P3vR2qPHDaZ6DX9-__bxZo7v7283N1zvkuRQzYhb7XnSShU6LXpEYlCek86IXQvRYOqFoCNoFrAm3WsUYOyFddCwy7HrPzsHF8W6L-HuJdTZjqj4Og81xWqpRmEolKGng53_A_bSU3LIZSiTFWDPeIHKEfJlqLbE3DyWNtjwZgs2hfXNs3xzkoX0jmufT6fDixhheHKe6G_DlBNjq7dAXm32qfzmKCZZCHTh65Gpb5W0sLwn___0ZzI6cMg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>216200834</pqid></control><display><type>article</type><title>High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Hagiwara, Satoshi ; Iwasaka, Hideo ; Matsumoto, Shigekiyo ; Noguchi, Takayuki</creator><creatorcontrib>Hagiwara, Satoshi ; Iwasaka, Hideo ; Matsumoto, Shigekiyo ; Noguchi, Takayuki</creatorcontrib><description>Objective
High mobility group box 1 (HMGB1) is an important factor in the development of sepsis. Previous work suggests that antithrombin III (ATIII) inhibits inflammation, but the mechanism of action is still poorly understood.
Design and setting
Prospective controlled animal study in a university laboratory.
Materials
Rats were randomly divided into a lipopolysaccharide (LPS)-induced sepsis control group and an ATIII-treated experimental group. Animals in the experimental group received a bolus of 250 units/kg of ATIII injected into the tail vein.
Measurements and results
Animals receiving high-dose ATIII (250 units/kg) had significantly improved lung histopathology and survival compared to the control rats. We measured serum and lung levels of various cytokines and HMGB1 at regular intervals from 0 to 12 h after the induction of sepsis and demonstrated lower HMGB1 levels over time in ATIII-treated animals. In an in vitro experiment, we stimulated the mouse macrophage cell line RAW 264.7 with LPS in the presence or absence of ATIII. Subsequent measurement of HMGB1 concentrations in the supernatant and cell signaling molecules in cell lysates revealed an ATIII dose-dependent decrease in HMGB1 release. Furthermore, inhibition of IkB and p42 phosphorylation was observed with the administration of ATIII, suggestive of downstream signaling pathways.
Conclusions
High-dose ATIII decreases lung pathology and reduces mortality in a rat sepsis model. This finding may be mediated by the inhibition of HMGB1.</description><identifier>ISSN: 0342-4642</identifier><identifier>EISSN: 1432-1238</identifier><identifier>DOI: 10.1007/s00134-007-0887-5</identifier><identifier>PMID: 17940748</identifier><identifier>CODEN: ICMED9</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Analysis of Variance ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Anesthesiology ; Animals ; Anticoagulants ; Antithrombin III - pharmacology ; Biological and medical sciences ; Blood. Blood coagulation. Reticuloendothelial system ; Blotting, Western ; Critical Care Medicine ; Cytokines ; Emergency Medicine ; Enzyme-Linked Immunosorbent Assay ; Experimental ; Histopathology ; HMGB1 Protein - drug effects ; Immunoenzyme Techniques ; Intensive ; Intensive care medicine ; Laboratory animals ; Lipopolysaccharides ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mortality ; Pain Medicine ; Pathogenesis ; Pediatrics ; Pharmacology. Drug treatments ; Pneumology/Respiratory System ; Prospective Studies ; Random Allocation ; Rats ; Rats, Wistar ; Respiratory Distress Syndrome, Adult - drug therapy ; Sepsis</subject><ispartof>Intensive care medicine, 2008-02, Vol.34 (2), p.361-367</ispartof><rights>Springer-Verlag 2007</rights><rights>2008 INIST-CNRS</rights><rights>Springer-Verlag 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-3a0cf5963d985f71ed7c119c5f555f06b572dd8bd0814a87eee956beb3e30bfc3</citedby><cites>FETCH-LOGICAL-c465t-3a0cf5963d985f71ed7c119c5f555f06b572dd8bd0814a87eee956beb3e30bfc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00134-007-0887-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00134-007-0887-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27907,27908,41471,42540,51302</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20106578$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17940748$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hagiwara, Satoshi</creatorcontrib><creatorcontrib>Iwasaka, Hideo</creatorcontrib><creatorcontrib>Matsumoto, Shigekiyo</creatorcontrib><creatorcontrib>Noguchi, Takayuki</creatorcontrib><title>High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats</title><title>Intensive care medicine</title><addtitle>Intensive Care Med</addtitle><addtitle>Intensive Care Med</addtitle><description>Objective
High mobility group box 1 (HMGB1) is an important factor in the development of sepsis. Previous work suggests that antithrombin III (ATIII) inhibits inflammation, but the mechanism of action is still poorly understood.
Design and setting
Prospective controlled animal study in a university laboratory.
Materials
Rats were randomly divided into a lipopolysaccharide (LPS)-induced sepsis control group and an ATIII-treated experimental group. Animals in the experimental group received a bolus of 250 units/kg of ATIII injected into the tail vein.
Measurements and results
Animals receiving high-dose ATIII (250 units/kg) had significantly improved lung histopathology and survival compared to the control rats. We measured serum and lung levels of various cytokines and HMGB1 at regular intervals from 0 to 12 h after the induction of sepsis and demonstrated lower HMGB1 levels over time in ATIII-treated animals. In an in vitro experiment, we stimulated the mouse macrophage cell line RAW 264.7 with LPS in the presence or absence of ATIII. Subsequent measurement of HMGB1 concentrations in the supernatant and cell signaling molecules in cell lysates revealed an ATIII dose-dependent decrease in HMGB1 release. Furthermore, inhibition of IkB and p42 phosphorylation was observed with the administration of ATIII, suggestive of downstream signaling pathways.
Conclusions
High-dose ATIII decreases lung pathology and reduces mortality in a rat sepsis model. This finding may be mediated by the inhibition of HMGB1.</description><subject>Analysis of Variance</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Anesthesiology</subject><subject>Animals</subject><subject>Anticoagulants</subject><subject>Antithrombin III - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Blotting, Western</subject><subject>Critical Care Medicine</subject><subject>Cytokines</subject><subject>Emergency Medicine</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Experimental</subject><subject>Histopathology</subject><subject>HMGB1 Protein - drug effects</subject><subject>Immunoenzyme Techniques</subject><subject>Intensive</subject><subject>Intensive care medicine</subject><subject>Laboratory animals</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mortality</subject><subject>Pain Medicine</subject><subject>Pathogenesis</subject><subject>Pediatrics</subject><subject>Pharmacology. Drug treatments</subject><subject>Pneumology/Respiratory System</subject><subject>Prospective Studies</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Respiratory Distress Syndrome, Adult - drug therapy</subject><subject>Sepsis</subject><issn>0342-4642</issn><issn>1432-1238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kN1rFDEUxYModq3-Ab5IEOxb2nwn82iLdhcqfdHnkK_ZzTKTqclMsf99s-xiQfDpHri_c-_hAPCR4EuCsbqqGBPGUZMIa62QeAVWhDOKCGX6NVhhxiniktMz8K7WfaOVFOQtOCOq41hxvQJunbY7GKYaoc1zmndlGl3KcLPZwJR3yaW5wvWP22vS9gGm8aFMj7HCmMM0T39SRimHxccArV_mCIclb5txv5SnNmCxc30P3vR2qPHDaZ6DX9-__bxZo7v7283N1zvkuRQzYhb7XnSShU6LXpEYlCek86IXQvRYOqFoCNoFrAm3WsUYOyFddCwy7HrPzsHF8W6L-HuJdTZjqj4Og81xWqpRmEolKGng53_A_bSU3LIZSiTFWDPeIHKEfJlqLbE3DyWNtjwZgs2hfXNs3xzkoX0jmufT6fDixhheHKe6G_DlBNjq7dAXm32qfzmKCZZCHTh65Gpb5W0sLwn___0ZzI6cMg</recordid><startdate>20080201</startdate><enddate>20080201</enddate><creator>Hagiwara, Satoshi</creator><creator>Iwasaka, Hideo</creator><creator>Matsumoto, Shigekiyo</creator><creator>Noguchi, Takayuki</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20080201</creationdate><title>High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats</title><author>Hagiwara, Satoshi ; Iwasaka, Hideo ; Matsumoto, Shigekiyo ; Noguchi, Takayuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-3a0cf5963d985f71ed7c119c5f555f06b572dd8bd0814a87eee956beb3e30bfc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Analysis of Variance</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Anesthesiology</topic><topic>Animals</topic><topic>Anticoagulants</topic><topic>Antithrombin III - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Blotting, Western</topic><topic>Critical Care Medicine</topic><topic>Cytokines</topic><topic>Emergency Medicine</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Experimental</topic><topic>Histopathology</topic><topic>HMGB1 Protein - drug effects</topic><topic>Immunoenzyme Techniques</topic><topic>Intensive</topic><topic>Intensive care medicine</topic><topic>Laboratory animals</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mortality</topic><topic>Pain Medicine</topic><topic>Pathogenesis</topic><topic>Pediatrics</topic><topic>Pharmacology. Drug treatments</topic><topic>Pneumology/Respiratory System</topic><topic>Prospective Studies</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Respiratory Distress Syndrome, Adult - drug therapy</topic><topic>Sepsis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hagiwara, Satoshi</creatorcontrib><creatorcontrib>Iwasaka, Hideo</creatorcontrib><creatorcontrib>Matsumoto, Shigekiyo</creatorcontrib><creatorcontrib>Noguchi, Takayuki</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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>MEDLINE - Academic</collection><jtitle>Intensive care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hagiwara, Satoshi</au><au>Iwasaka, Hideo</au><au>Matsumoto, Shigekiyo</au><au>Noguchi, Takayuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats</atitle><jtitle>Intensive care medicine</jtitle><stitle>Intensive Care Med</stitle><addtitle>Intensive Care Med</addtitle><date>2008-02-01</date><risdate>2008</risdate><volume>34</volume><issue>2</issue><spage>361</spage><epage>367</epage><pages>361-367</pages><issn>0342-4642</issn><eissn>1432-1238</eissn><coden>ICMED9</coden><abstract>Objective
High mobility group box 1 (HMGB1) is an important factor in the development of sepsis. Previous work suggests that antithrombin III (ATIII) inhibits inflammation, but the mechanism of action is still poorly understood.
Design and setting
Prospective controlled animal study in a university laboratory.
Materials
Rats were randomly divided into a lipopolysaccharide (LPS)-induced sepsis control group and an ATIII-treated experimental group. Animals in the experimental group received a bolus of 250 units/kg of ATIII injected into the tail vein.
Measurements and results
Animals receiving high-dose ATIII (250 units/kg) had significantly improved lung histopathology and survival compared to the control rats. We measured serum and lung levels of various cytokines and HMGB1 at regular intervals from 0 to 12 h after the induction of sepsis and demonstrated lower HMGB1 levels over time in ATIII-treated animals. In an in vitro experiment, we stimulated the mouse macrophage cell line RAW 264.7 with LPS in the presence or absence of ATIII. Subsequent measurement of HMGB1 concentrations in the supernatant and cell signaling molecules in cell lysates revealed an ATIII dose-dependent decrease in HMGB1 release. Furthermore, inhibition of IkB and p42 phosphorylation was observed with the administration of ATIII, suggestive of downstream signaling pathways.
Conclusions
High-dose ATIII decreases lung pathology and reduces mortality in a rat sepsis model. This finding may be mediated by the inhibition of HMGB1.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>17940748</pmid><doi>10.1007/s00134-007-0887-5</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0342-4642 |
| ispartof | Intensive care medicine, 2008-02, Vol.34 (2), p.361-367 |
| issn | 0342-4642 1432-1238 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70267521 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Analysis of Variance Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Anesthesiology Animals Anticoagulants Antithrombin III - pharmacology Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Blotting, Western Critical Care Medicine Cytokines Emergency Medicine Enzyme-Linked Immunosorbent Assay Experimental Histopathology HMGB1 Protein - drug effects Immunoenzyme Techniques Intensive Intensive care medicine Laboratory animals Lipopolysaccharides Male Medical sciences Medicine Medicine & Public Health Mortality Pain Medicine Pathogenesis Pediatrics Pharmacology. Drug treatments Pneumology/Respiratory System Prospective Studies Random Allocation Rats Rats, Wistar Respiratory Distress Syndrome, Adult - drug therapy Sepsis |
| title | High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T08%3A44%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20dose%20antithrombin%20III%20inhibits%20HMGB1%20and%20improves%20endotoxin-induced%20acute%20lung%20injury%20in%20rats&rft.jtitle=Intensive%20care%20medicine&rft.au=Hagiwara,%20Satoshi&rft.date=2008-02-01&rft.volume=34&rft.issue=2&rft.spage=361&rft.epage=367&rft.pages=361-367&rft.issn=0342-4642&rft.eissn=1432-1238&rft.coden=ICMED9&rft_id=info:doi/10.1007/s00134-007-0887-5&rft_dat=%3Cproquest_cross%3E1432002771%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=216200834&rft_id=info:pmid/17940748&rfr_iscdi=true |