The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury
Background and objective Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related morbidity and mortality. Specific therapy is lacking. We assessed whether C1‐inhibitor attenuates lung injury in a ‘two‐hit’ TRALI model. Methods Mice were primed with lipopolysaccharid...
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| Veröffentlicht in: | Vox sanguinis 2014-07, Vol.107 (1), p.71-75 |
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| creator | Müller, M. C. A. Stroo, I. Wouters, D. Zeerleder, S. S. Roelofs, J. J. T. H. Boon, L. Vroom, M. B. Juffermans, N. P. |
| description | Background and objective
Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related morbidity and mortality. Specific therapy is lacking. We assessed whether C1‐inhibitor attenuates lung injury in a ‘two‐hit’ TRALI model.
Methods
Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC‐I antibodies. In the intervention group, C1‐inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained.
Results
Injection of MHC‐I antibodies induced TRALI, illustrated by an increase in wet‐to‐dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1‐inhibitor resulted in increased pulmonary C1‐inhibitor levels with high activity. C1‐inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro‐inflammatory mediators were unaffected.
Conclusion
In a murine model of TRALI, C1‐inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines. |
| doi_str_mv | 10.1111/vox.12128 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1535626049</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1535626049</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3918-c687171d1c0d4861efea92e166a2a6b3eed03a4e6836a44856452306b8fa12853</originalsourceid><addsrcrecordid>eNp1kE1PGzEQhi1E1aRpD_wBZIlLe9jE3-scUWhoKxQukPZmObuz4LC7DvYayL_vhhAOlTqXuTzvo5kXoRNKxrSfyZN_GVNGmT5CQyoYz4ig5BgNCREsmxKSD9CnGNeEEM20_IgGTPCcccaH6PbmHjBUFRQd9hWe0cy1927lOh-wa7HFTQquBdz4Euod0QXbxipF59ssQG07KLEtUge4Tu1dn1mnsP2MPlS2jvDlbY_Q7fz7zexHdnV9-XN2fpUVfEp1Viid05yWtCCl0IpCBXbKgCplmVUrDlASbgUozZUVQkslJONErXRl-28lH6Gve-8m-McEsTONiwXUtW3Bp2io5FIxRcS0R8_-Qdc-hba_7pViRGu5E37bU0XwMQaozCa4xoatocTsujZ91-a16549fTOmVQPlO3kotwcme-DZ1bD9v8ksr_8clNk-4WIHL-8JGx6Mynkuze_Fpfl1sZjPlVyaBf8Lw0KVjg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1535208855</pqid></control><display><type>article</type><title>The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Müller, M. C. A. ; Stroo, I. ; Wouters, D. ; Zeerleder, S. S. ; Roelofs, J. J. T. H. ; Boon, L. ; Vroom, M. B. ; Juffermans, N. P.</creator><creatorcontrib>Müller, M. C. A. ; Stroo, I. ; Wouters, D. ; Zeerleder, S. S. ; Roelofs, J. J. T. H. ; Boon, L. ; Vroom, M. B. ; Juffermans, N. P.</creatorcontrib><description>Background and objective
Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related morbidity and mortality. Specific therapy is lacking. We assessed whether C1‐inhibitor attenuates lung injury in a ‘two‐hit’ TRALI model.
Methods
Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC‐I antibodies. In the intervention group, C1‐inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained.
Results
Injection of MHC‐I antibodies induced TRALI, illustrated by an increase in wet‐to‐dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1‐inhibitor resulted in increased pulmonary C1‐inhibitor levels with high activity. C1‐inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro‐inflammatory mediators were unaffected.
Conclusion
In a murine model of TRALI, C1‐inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.</description><identifier>ISSN: 0042-9007</identifier><identifier>EISSN: 1423-0410</identifier><identifier>DOI: 10.1111/vox.12128</identifier><identifier>PMID: 24372323</identifier><identifier>CODEN: VOSAAD</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Acute Lung Injury - drug therapy ; Acute Lung Injury - etiology ; Acute Lung Injury - pathology ; Analysis of Variance ; Animals ; Antibodies - immunology ; Blood transfusions ; Bronchoalveolar Lavage Fluid - immunology ; C1-inhibitor ; complement ; Complement Activation - immunology ; Complement C1 Inhibitor Protein - administration & dosage ; Complement C3a - immunology ; Complement C5a - immunology ; Cytokines ; Cytokines - immunology ; Disease Models, Animal ; Lipopolysaccharides ; Lung - metabolism ; Lung - pathology ; Lungs ; Male ; MHC-I antibody ; Mice ; Mice, Inbred BALB C ; Morbidity ; Mortality ; Rodents ; transfusion ; Transfusion Reaction - drug therapy ; Transfusion Reaction - pathology ; transfusion-related acute lung injury</subject><ispartof>Vox sanguinis, 2014-07, Vol.107 (1), p.71-75</ispartof><rights>2013 International Society of Blood Transfusion</rights><rights>2013 International Society of Blood Transfusion.</rights><rights>Copyright Vox Sanguinis © 2014 International Society of Blood Transfusion</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3918-c687171d1c0d4861efea92e166a2a6b3eed03a4e6836a44856452306b8fa12853</citedby><cites>FETCH-LOGICAL-c3918-c687171d1c0d4861efea92e166a2a6b3eed03a4e6836a44856452306b8fa12853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fvox.12128$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fvox.12128$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24372323$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Müller, M. C. A.</creatorcontrib><creatorcontrib>Stroo, I.</creatorcontrib><creatorcontrib>Wouters, D.</creatorcontrib><creatorcontrib>Zeerleder, S. S.</creatorcontrib><creatorcontrib>Roelofs, J. J. T. H.</creatorcontrib><creatorcontrib>Boon, L.</creatorcontrib><creatorcontrib>Vroom, M. B.</creatorcontrib><creatorcontrib>Juffermans, N. P.</creatorcontrib><title>The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury</title><title>Vox sanguinis</title><addtitle>Vox Sang</addtitle><description>Background and objective
Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related morbidity and mortality. Specific therapy is lacking. We assessed whether C1‐inhibitor attenuates lung injury in a ‘two‐hit’ TRALI model.
Methods
Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC‐I antibodies. In the intervention group, C1‐inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained.
Results
Injection of MHC‐I antibodies induced TRALI, illustrated by an increase in wet‐to‐dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1‐inhibitor resulted in increased pulmonary C1‐inhibitor levels with high activity. C1‐inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro‐inflammatory mediators were unaffected.
Conclusion
In a murine model of TRALI, C1‐inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.</description><subject>Acute Lung Injury - drug therapy</subject><subject>Acute Lung Injury - etiology</subject><subject>Acute Lung Injury - pathology</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Antibodies - immunology</subject><subject>Blood transfusions</subject><subject>Bronchoalveolar Lavage Fluid - immunology</subject><subject>C1-inhibitor</subject><subject>complement</subject><subject>Complement Activation - immunology</subject><subject>Complement C1 Inhibitor Protein - administration & dosage</subject><subject>Complement C3a - immunology</subject><subject>Complement C5a - immunology</subject><subject>Cytokines</subject><subject>Cytokines - immunology</subject><subject>Disease Models, Animal</subject><subject>Lipopolysaccharides</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lungs</subject><subject>Male</subject><subject>MHC-I antibody</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Rodents</subject><subject>transfusion</subject><subject>Transfusion Reaction - drug therapy</subject><subject>Transfusion Reaction - pathology</subject><subject>transfusion-related acute lung injury</subject><issn>0042-9007</issn><issn>1423-0410</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1PGzEQhi1E1aRpD_wBZIlLe9jE3-scUWhoKxQukPZmObuz4LC7DvYayL_vhhAOlTqXuTzvo5kXoRNKxrSfyZN_GVNGmT5CQyoYz4ig5BgNCREsmxKSD9CnGNeEEM20_IgGTPCcccaH6PbmHjBUFRQd9hWe0cy1927lOh-wa7HFTQquBdz4Euod0QXbxipF59ssQG07KLEtUge4Tu1dn1mnsP2MPlS2jvDlbY_Q7fz7zexHdnV9-XN2fpUVfEp1Viid05yWtCCl0IpCBXbKgCplmVUrDlASbgUozZUVQkslJONErXRl-28lH6Gve-8m-McEsTONiwXUtW3Bp2io5FIxRcS0R8_-Qdc-hba_7pViRGu5E37bU0XwMQaozCa4xoatocTsujZ91-a16549fTOmVQPlO3kotwcme-DZ1bD9v8ksr_8clNk-4WIHL-8JGx6Mynkuze_Fpfl1sZjPlVyaBf8Lw0KVjg</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Müller, M. C. A.</creator><creator>Stroo, I.</creator><creator>Wouters, D.</creator><creator>Zeerleder, S. S.</creator><creator>Roelofs, J. J. T. H.</creator><creator>Boon, L.</creator><creator>Vroom, M. B.</creator><creator>Juffermans, N. P.</creator><general>Blackwell Publishing Ltd</general><general>S. Karger AG</general><scope>BSCLL</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>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>201407</creationdate><title>The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury</title><author>Müller, M. C. A. ; Stroo, I. ; Wouters, D. ; Zeerleder, S. S. ; Roelofs, J. J. T. H. ; Boon, L. ; Vroom, M. B. ; Juffermans, N. P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3918-c687171d1c0d4861efea92e166a2a6b3eed03a4e6836a44856452306b8fa12853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acute Lung Injury - drug therapy</topic><topic>Acute Lung Injury - etiology</topic><topic>Acute Lung Injury - pathology</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Antibodies - immunology</topic><topic>Blood transfusions</topic><topic>Bronchoalveolar Lavage Fluid - immunology</topic><topic>C1-inhibitor</topic><topic>complement</topic><topic>Complement Activation - immunology</topic><topic>Complement C1 Inhibitor Protein - administration & dosage</topic><topic>Complement C3a - immunology</topic><topic>Complement C5a - immunology</topic><topic>Cytokines</topic><topic>Cytokines - immunology</topic><topic>Disease Models, Animal</topic><topic>Lipopolysaccharides</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Lungs</topic><topic>Male</topic><topic>MHC-I antibody</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Rodents</topic><topic>transfusion</topic><topic>Transfusion Reaction - drug therapy</topic><topic>Transfusion Reaction - pathology</topic><topic>transfusion-related acute lung injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Müller, M. C. A.</creatorcontrib><creatorcontrib>Stroo, I.</creatorcontrib><creatorcontrib>Wouters, D.</creatorcontrib><creatorcontrib>Zeerleder, S. S.</creatorcontrib><creatorcontrib>Roelofs, J. J. T. H.</creatorcontrib><creatorcontrib>Boon, L.</creatorcontrib><creatorcontrib>Vroom, M. B.</creatorcontrib><creatorcontrib>Juffermans, N. P.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Vox sanguinis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Müller, M. C. A.</au><au>Stroo, I.</au><au>Wouters, D.</au><au>Zeerleder, S. S.</au><au>Roelofs, J. J. T. H.</au><au>Boon, L.</au><au>Vroom, M. B.</au><au>Juffermans, N. P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury</atitle><jtitle>Vox sanguinis</jtitle><addtitle>Vox Sang</addtitle><date>2014-07</date><risdate>2014</risdate><volume>107</volume><issue>1</issue><spage>71</spage><epage>75</epage><pages>71-75</pages><issn>0042-9007</issn><eissn>1423-0410</eissn><coden>VOSAAD</coden><abstract>Background and objective
Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related morbidity and mortality. Specific therapy is lacking. We assessed whether C1‐inhibitor attenuates lung injury in a ‘two‐hit’ TRALI model.
Methods
Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC‐I antibodies. In the intervention group, C1‐inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained.
Results
Injection of MHC‐I antibodies induced TRALI, illustrated by an increase in wet‐to‐dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1‐inhibitor resulted in increased pulmonary C1‐inhibitor levels with high activity. C1‐inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro‐inflammatory mediators were unaffected.
Conclusion
In a murine model of TRALI, C1‐inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>24372323</pmid><doi>10.1111/vox.12128</doi><tpages>5</tpages></addata></record> |
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| subjects | Acute Lung Injury - drug therapy Acute Lung Injury - etiology Acute Lung Injury - pathology Analysis of Variance Animals Antibodies - immunology Blood transfusions Bronchoalveolar Lavage Fluid - immunology C1-inhibitor complement Complement Activation - immunology Complement C1 Inhibitor Protein - administration & dosage Complement C3a - immunology Complement C5a - immunology Cytokines Cytokines - immunology Disease Models, Animal Lipopolysaccharides Lung - metabolism Lung - pathology Lungs Male MHC-I antibody Mice Mice, Inbred BALB C Morbidity Mortality Rodents transfusion Transfusion Reaction - drug therapy Transfusion Reaction - pathology transfusion-related acute lung injury |
| title | The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury |
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