Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis
Leukotriene B4 (LTB4) is a chemotactic and cell-activating factor present at inflammatory sites in a variety of autoimmune diseases including multiple sclerosis (MS). In this study, we used a murine model of MS, experimental allergic encephalomyelitis (EAE), to assess the potential role of LTB4 on c...
Gespeichert in:
| Veröffentlicht in: | The Journal of experimental medicine 1996-04, Vol.183 (4), p.1893-1898 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1898 |
|---|---|
| container_issue | 4 |
| container_start_page | 1893 |
| container_title | The Journal of experimental medicine |
| container_volume | 183 |
| creator | Gladue, R P Carroll, L A Milici, A J Scampoli, D N Stukenbrok, H A Pettipher, E R Salter, E D Contillo, L Showell, H J |
| description | Leukotriene B4 (LTB4) is a chemotactic and cell-activating factor present at inflammatory sites in a variety of autoimmune diseases including multiple sclerosis (MS). In this study, we used a murine model of MS, experimental allergic encephalomyelitis (EAE), to assess the potential role of LTB4 on cell infiltration and paralysis. Injection of encephalogenic T cells into naive animals induced paralysis and weight loss that was completely inhibited by treatment with the selective LTB4 receptor antagonist CP-105,696 (ED50= 8.6 mg/kg orally). Although migration of lymphocytes into the central nervous system was unaffected, the efficacious effects of CP-105,696 correlated with up to a 97% decrease in eosinophil infiltration into the lower spinal cord as determined by light and electron microscopy and quantitated by levels of the specific enzyme marker eosinophil peroxidase. These results demonstrate that eosinophil recruitment in EAE is dependent on LTB4 receptor ligation and further reveal a previously unrecognized role for eosinophils in the pathogenesis of this disease. |
| doi_str_mv | 10.1084/jem.183.4.1893 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2192487</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>78118995</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3663-4ea7881a190cc1721817cdc92476e8d418e600e5c1f303ad30db52e12efd569e3</originalsourceid><addsrcrecordid>eNpVkTFv3CAYhlHVKr1cu3arxNTNFzAY46VScmqTSJG6tDPi4POZFIMLdtT7Rf2b5ZJTlCww8PC-r_Qg9ImSDSWSX9zDuKGSbXg5O_YGrWjDSdU1TL5FK0LquqKEtO_Rec73hFDOG3GGzqQQouPNCv27DYPbudnFgGOPPSy_45wcBMBXvEpgYJpjwi7MkLR5xPIyTQlyhowhZhfiNDhfiN75OelHRAeLrcugM-BJz0P0cX8oCNZ4XJIr4WO04I-N8HeC5EYIs_ZYew9p7wyGUIoH7eN4AF_W5Q_oXa99ho-ne41-ff_2c3tT3f24vt1e3lWGCcEqDrqVkmraEWNoW1NJW2NNV_NWgLScShCEQGNozwjTlhG7a2qgNfS2ER2wNfr6lDstuxGsKbuS9moqE3U6qKidev0S3KD28UHVtJTItgR8OQWk-GeBPKvRZQPe6wBxyaqVtIgqftZo8wSaFHNO0D-XUKKOalVRq4paxdVRbfnw-eW0Z_zkkv0HFjumfA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>78118995</pqid></control><display><type>article</type><title>Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Gladue, R P ; Carroll, L A ; Milici, A J ; Scampoli, D N ; Stukenbrok, H A ; Pettipher, E R ; Salter, E D ; Contillo, L ; Showell, H J</creator><creatorcontrib>Gladue, R P ; Carroll, L A ; Milici, A J ; Scampoli, D N ; Stukenbrok, H A ; Pettipher, E R ; Salter, E D ; Contillo, L ; Showell, H J</creatorcontrib><description>Leukotriene B4 (LTB4) is a chemotactic and cell-activating factor present at inflammatory sites in a variety of autoimmune diseases including multiple sclerosis (MS). In this study, we used a murine model of MS, experimental allergic encephalomyelitis (EAE), to assess the potential role of LTB4 on cell infiltration and paralysis. Injection of encephalogenic T cells into naive animals induced paralysis and weight loss that was completely inhibited by treatment with the selective LTB4 receptor antagonist CP-105,696 (ED50= 8.6 mg/kg orally). Although migration of lymphocytes into the central nervous system was unaffected, the efficacious effects of CP-105,696 correlated with up to a 97% decrease in eosinophil infiltration into the lower spinal cord as determined by light and electron microscopy and quantitated by levels of the specific enzyme marker eosinophil peroxidase. These results demonstrate that eosinophil recruitment in EAE is dependent on LTB4 receptor ligation and further reveal a previously unrecognized role for eosinophils in the pathogenesis of this disease.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.183.4.1893</identifier><identifier>PMID: 8666945</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Amino Acid Sequence ; Animals ; Benzopyrans - pharmacology ; Benzopyrans - therapeutic use ; Carboxylic Acids - pharmacology ; Carboxylic Acids - therapeutic use ; Cell Movement - drug effects ; Encephalomyelitis, Autoimmune, Experimental - etiology ; Encephalomyelitis, Autoimmune, Experimental - pathology ; Encephalomyelitis, Autoimmune, Experimental - prevention & control ; Eosinophils - drug effects ; Female ; Immunization, Passive ; Mice ; Mice, Inbred Strains ; Molecular Sequence Data ; Oligopeptides - immunology ; Paralysis - prevention & control ; Receptors, Leukotriene B4 - antagonists & inhibitors ; Spinal Cord - pathology ; T-Lymphocytes - immunology</subject><ispartof>The Journal of experimental medicine, 1996-04, Vol.183 (4), p.1893-1898</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3663-4ea7881a190cc1721817cdc92476e8d418e600e5c1f303ad30db52e12efd569e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8666945$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gladue, R P</creatorcontrib><creatorcontrib>Carroll, L A</creatorcontrib><creatorcontrib>Milici, A J</creatorcontrib><creatorcontrib>Scampoli, D N</creatorcontrib><creatorcontrib>Stukenbrok, H A</creatorcontrib><creatorcontrib>Pettipher, E R</creatorcontrib><creatorcontrib>Salter, E D</creatorcontrib><creatorcontrib>Contillo, L</creatorcontrib><creatorcontrib>Showell, H J</creatorcontrib><title>Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Leukotriene B4 (LTB4) is a chemotactic and cell-activating factor present at inflammatory sites in a variety of autoimmune diseases including multiple sclerosis (MS). In this study, we used a murine model of MS, experimental allergic encephalomyelitis (EAE), to assess the potential role of LTB4 on cell infiltration and paralysis. Injection of encephalogenic T cells into naive animals induced paralysis and weight loss that was completely inhibited by treatment with the selective LTB4 receptor antagonist CP-105,696 (ED50= 8.6 mg/kg orally). Although migration of lymphocytes into the central nervous system was unaffected, the efficacious effects of CP-105,696 correlated with up to a 97% decrease in eosinophil infiltration into the lower spinal cord as determined by light and electron microscopy and quantitated by levels of the specific enzyme marker eosinophil peroxidase. These results demonstrate that eosinophil recruitment in EAE is dependent on LTB4 receptor ligation and further reveal a previously unrecognized role for eosinophils in the pathogenesis of this disease.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Benzopyrans - pharmacology</subject><subject>Benzopyrans - therapeutic use</subject><subject>Carboxylic Acids - pharmacology</subject><subject>Carboxylic Acids - therapeutic use</subject><subject>Cell Movement - drug effects</subject><subject>Encephalomyelitis, Autoimmune, Experimental - etiology</subject><subject>Encephalomyelitis, Autoimmune, Experimental - pathology</subject><subject>Encephalomyelitis, Autoimmune, Experimental - prevention & control</subject><subject>Eosinophils - drug effects</subject><subject>Female</subject><subject>Immunization, Passive</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Molecular Sequence Data</subject><subject>Oligopeptides - immunology</subject><subject>Paralysis - prevention & control</subject><subject>Receptors, Leukotriene B4 - antagonists & inhibitors</subject><subject>Spinal Cord - pathology</subject><subject>T-Lymphocytes - immunology</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkTFv3CAYhlHVKr1cu3arxNTNFzAY46VScmqTSJG6tDPi4POZFIMLdtT7Rf2b5ZJTlCww8PC-r_Qg9ImSDSWSX9zDuKGSbXg5O_YGrWjDSdU1TL5FK0LquqKEtO_Rec73hFDOG3GGzqQQouPNCv27DYPbudnFgGOPPSy_45wcBMBXvEpgYJpjwi7MkLR5xPIyTQlyhowhZhfiNDhfiN75OelHRAeLrcugM-BJz0P0cX8oCNZ4XJIr4WO04I-N8HeC5EYIs_ZYew9p7wyGUIoH7eN4AF_W5Q_oXa99ho-ne41-ff_2c3tT3f24vt1e3lWGCcEqDrqVkmraEWNoW1NJW2NNV_NWgLScShCEQGNozwjTlhG7a2qgNfS2ER2wNfr6lDstuxGsKbuS9moqE3U6qKidev0S3KD28UHVtJTItgR8OQWk-GeBPKvRZQPe6wBxyaqVtIgqftZo8wSaFHNO0D-XUKKOalVRq4paxdVRbfnw-eW0Z_zkkv0HFjumfA</recordid><startdate>19960401</startdate><enddate>19960401</enddate><creator>Gladue, R P</creator><creator>Carroll, L A</creator><creator>Milici, A J</creator><creator>Scampoli, D N</creator><creator>Stukenbrok, H A</creator><creator>Pettipher, E R</creator><creator>Salter, E D</creator><creator>Contillo, L</creator><creator>Showell, H J</creator><general>The Rockefeller University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960401</creationdate><title>Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis</title><author>Gladue, R P ; Carroll, L A ; Milici, A J ; Scampoli, D N ; Stukenbrok, H A ; Pettipher, E R ; Salter, E D ; Contillo, L ; Showell, H J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3663-4ea7881a190cc1721817cdc92476e8d418e600e5c1f303ad30db52e12efd569e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Benzopyrans - pharmacology</topic><topic>Benzopyrans - therapeutic use</topic><topic>Carboxylic Acids - pharmacology</topic><topic>Carboxylic Acids - therapeutic use</topic><topic>Cell Movement - drug effects</topic><topic>Encephalomyelitis, Autoimmune, Experimental - etiology</topic><topic>Encephalomyelitis, Autoimmune, Experimental - pathology</topic><topic>Encephalomyelitis, Autoimmune, Experimental - prevention & control</topic><topic>Eosinophils - drug effects</topic><topic>Female</topic><topic>Immunization, Passive</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Molecular Sequence Data</topic><topic>Oligopeptides - immunology</topic><topic>Paralysis - prevention & control</topic><topic>Receptors, Leukotriene B4 - antagonists & inhibitors</topic><topic>Spinal Cord - pathology</topic><topic>T-Lymphocytes - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gladue, R P</creatorcontrib><creatorcontrib>Carroll, L A</creatorcontrib><creatorcontrib>Milici, A J</creatorcontrib><creatorcontrib>Scampoli, D N</creatorcontrib><creatorcontrib>Stukenbrok, H A</creatorcontrib><creatorcontrib>Pettipher, E R</creatorcontrib><creatorcontrib>Salter, E D</creatorcontrib><creatorcontrib>Contillo, L</creatorcontrib><creatorcontrib>Showell, H J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gladue, R P</au><au>Carroll, L A</au><au>Milici, A J</au><au>Scampoli, D N</au><au>Stukenbrok, H A</au><au>Pettipher, E R</au><au>Salter, E D</au><au>Contillo, L</au><au>Showell, H J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>1996-04-01</date><risdate>1996</risdate><volume>183</volume><issue>4</issue><spage>1893</spage><epage>1898</epage><pages>1893-1898</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Leukotriene B4 (LTB4) is a chemotactic and cell-activating factor present at inflammatory sites in a variety of autoimmune diseases including multiple sclerosis (MS). In this study, we used a murine model of MS, experimental allergic encephalomyelitis (EAE), to assess the potential role of LTB4 on cell infiltration and paralysis. Injection of encephalogenic T cells into naive animals induced paralysis and weight loss that was completely inhibited by treatment with the selective LTB4 receptor antagonist CP-105,696 (ED50= 8.6 mg/kg orally). Although migration of lymphocytes into the central nervous system was unaffected, the efficacious effects of CP-105,696 correlated with up to a 97% decrease in eosinophil infiltration into the lower spinal cord as determined by light and electron microscopy and quantitated by levels of the specific enzyme marker eosinophil peroxidase. These results demonstrate that eosinophil recruitment in EAE is dependent on LTB4 receptor ligation and further reveal a previously unrecognized role for eosinophils in the pathogenesis of this disease.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>8666945</pmid><doi>10.1084/jem.183.4.1893</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1007 |
| ispartof | The Journal of experimental medicine, 1996-04, Vol.183 (4), p.1893-1898 |
| issn | 0022-1007 1540-9538 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2192487 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Amino Acid Sequence Animals Benzopyrans - pharmacology Benzopyrans - therapeutic use Carboxylic Acids - pharmacology Carboxylic Acids - therapeutic use Cell Movement - drug effects Encephalomyelitis, Autoimmune, Experimental - etiology Encephalomyelitis, Autoimmune, Experimental - pathology Encephalomyelitis, Autoimmune, Experimental - prevention & control Eosinophils - drug effects Female Immunization, Passive Mice Mice, Inbred Strains Molecular Sequence Data Oligopeptides - immunology Paralysis - prevention & control Receptors, Leukotriene B4 - antagonists & inhibitors Spinal Cord - pathology T-Lymphocytes - immunology |
| title | Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T17%3A55%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20leukotriene%20B4-receptor%20interaction%20suppresses%20eosinophil%20infiltration%20and%20disease%20pathology%20in%20a%20murine%20model%20of%20experimental%20allergic%20encephalomyelitis&rft.jtitle=The%20Journal%20of%20experimental%20medicine&rft.au=Gladue,%20R%20P&rft.date=1996-04-01&rft.volume=183&rft.issue=4&rft.spage=1893&rft.epage=1898&rft.pages=1893-1898&rft.issn=0022-1007&rft.eissn=1540-9538&rft_id=info:doi/10.1084/jem.183.4.1893&rft_dat=%3Cproquest_pubme%3E78118995%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=78118995&rft_id=info:pmid/8666945&rfr_iscdi=true |