Inhibition of polymorphonuclear leukocyte-mediated graft damage synergizes with short-term costimulatory blockade to prevent cardiac allograft rejection
The early inflammatory response during reperfusion of cardiac allografts is initiated by the infiltration of polymorphonuclear leukocytes (PMNs) into the graft. The impact of early PMN infiltration on allograft rejection compared with long-term graft survival remains poorly understood. We tested the...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2005-07, Vol.112 (3), p.320-331 |
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| creator | EL-SAWY, Tarek BELPERIO, John A STRIETER, Robert M REMICK, Daniel G FAIRCHILD, Robert L |
| description | The early inflammatory response during reperfusion of cardiac allografts is initiated by the infiltration of polymorphonuclear leukocytes (PMNs) into the graft. The impact of early PMN infiltration on allograft rejection compared with long-term graft survival remains poorly understood.
We tested the role of CXCR2, the receptor for 2 PMN attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and vascularized cardiac allograft rejection in a murine model. Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera-treated wild-type or from CXCR2(-/-) recipients. Adoptive transfer of alloantigen-primed T cells rapidly infiltrated and rejected allografts in control recipients, but T-cell infiltration was significantly decreased in recipients depleted of PMNs at transplantation. The influence of early PMN-mediated inflammation on the therapeutic efficacy of costimulatory blockade to prevent allograft rejection was tested. Short-term treatment of recipients with anti-CD154 mAb or CTLA-4 Ig induced modest prolongation of cardiac allograft survival. However, CD154 mAb or CTLA-4 Ig treatment, combined with either peritransplantation PMN depletion or antibodies specific for KC/CXCL1 plus MIP-2/CXCL2, prolonged cardiac allograft survival beyond 100 days.
Results suggest that strategies attenuating PMN-mediated tissue damage during reperfusion significantly improve the efficacy of short-term costimulatory blockade to prevent T-cell-mediated rejection of cardiac allografts. |
| doi_str_mv | 10.1161/CIRCULATIONAHA.104.516708 |
| format | Article |
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We tested the role of CXCR2, the receptor for 2 PMN attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and vascularized cardiac allograft rejection in a murine model. Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera-treated wild-type or from CXCR2(-/-) recipients. Adoptive transfer of alloantigen-primed T cells rapidly infiltrated and rejected allografts in control recipients, but T-cell infiltration was significantly decreased in recipients depleted of PMNs at transplantation. The influence of early PMN-mediated inflammation on the therapeutic efficacy of costimulatory blockade to prevent allograft rejection was tested. Short-term treatment of recipients with anti-CD154 mAb or CTLA-4 Ig induced modest prolongation of cardiac allograft survival. However, CD154 mAb or CTLA-4 Ig treatment, combined with either peritransplantation PMN depletion or antibodies specific for KC/CXCL1 plus MIP-2/CXCL2, prolonged cardiac allograft survival beyond 100 days.
Results suggest that strategies attenuating PMN-mediated tissue damage during reperfusion significantly improve the efficacy of short-term costimulatory blockade to prevent T-cell-mediated rejection of cardiac allografts.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.104.516708</identifier><identifier>PMID: 15998678</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Abatacept ; Animals ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; CD40 Ligand - physiology ; CD8-Positive T-Lymphocytes - immunology ; Cytokines - biosynthesis ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Endothelial Cells - physiology ; Graft Rejection - prevention & control ; Graft Survival ; Heart ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Heart Transplantation - immunology ; Immunoconjugates - pharmacology ; Immunologic Memory ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neutrophil Infiltration ; Neutrophils - physiology ; Receptors, Interleukin-8B - antagonists & inhibitors ; Receptors, Interleukin-8B - physiology ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart ; Transplantation, Homologous</subject><ispartof>Circulation (New York, N.Y.), 2005-07, Vol.112 (3), p.320-331</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-51106e754fd4d5b4f64bceb41d7b6ca931f17f6869dcc940e36334650e1ee1723</citedby><cites>FETCH-LOGICAL-c468t-51106e754fd4d5b4f64bceb41d7b6ca931f17f6869dcc940e36334650e1ee1723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3685,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16987093$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15998678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EL-SAWY, Tarek</creatorcontrib><creatorcontrib>BELPERIO, John A</creatorcontrib><creatorcontrib>STRIETER, Robert M</creatorcontrib><creatorcontrib>REMICK, Daniel G</creatorcontrib><creatorcontrib>FAIRCHILD, Robert L</creatorcontrib><title>Inhibition of polymorphonuclear leukocyte-mediated graft damage synergizes with short-term costimulatory blockade to prevent cardiac allograft rejection</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The early inflammatory response during reperfusion of cardiac allografts is initiated by the infiltration of polymorphonuclear leukocytes (PMNs) into the graft. The impact of early PMN infiltration on allograft rejection compared with long-term graft survival remains poorly understood.
We tested the role of CXCR2, the receptor for 2 PMN attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and vascularized cardiac allograft rejection in a murine model. Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera-treated wild-type or from CXCR2(-/-) recipients. Adoptive transfer of alloantigen-primed T cells rapidly infiltrated and rejected allografts in control recipients, but T-cell infiltration was significantly decreased in recipients depleted of PMNs at transplantation. The influence of early PMN-mediated inflammation on the therapeutic efficacy of costimulatory blockade to prevent allograft rejection was tested. Short-term treatment of recipients with anti-CD154 mAb or CTLA-4 Ig induced modest prolongation of cardiac allograft survival. However, CD154 mAb or CTLA-4 Ig treatment, combined with either peritransplantation PMN depletion or antibodies specific for KC/CXCL1 plus MIP-2/CXCL2, prolonged cardiac allograft survival beyond 100 days.
Results suggest that strategies attenuating PMN-mediated tissue damage during reperfusion significantly improve the efficacy of short-term costimulatory blockade to prevent T-cell-mediated rejection of cardiac allografts.</description><subject>Abatacept</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>CD40 Ligand - physiology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cytokines - biosynthesis</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Endothelial Cells - physiology</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival</subject><subject>Heart</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Heart Transplantation - immunology</subject><subject>Immunoconjugates - pharmacology</subject><subject>Immunologic Memory</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Neutrophil Infiltration</subject><subject>Neutrophils - physiology</subject><subject>Receptors, Interleukin-8B - antagonists & inhibitors</subject><subject>Receptors, Interleukin-8B - physiology</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><subject>Transplantation, Homologous</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkcGO0zAQhi0EYsvCKyBzgFuKJ3bs-FhVwFaqWAntniPHmbTedeJiO6DwJDwuWbXSitNoRt__z2h-Qj4AWwNI-Lzd_dje7zd3u9vvm5vNGphYVyAVq1-QFVSlKETF9UuyYozpQvGyvCJvUnpYWslV9ZpcQaV1LVW9In9349G1Lrsw0tDTU_DzEOLpGMbJejSRepweg50zFgN2zmTs6CGaPtPODOaANM0jxoP7g4n-dvlI0zHEXGSMA7UhZTdM3uQQZ9r6YB9NhzQHeor4C8dMrYmLp6XG-3B2jfiA9umat-RVb3zCd5d6Te6_frnb3hT722-77WZfWCHrXFQATKKqRN-JrmpFL0VrsRXQqVZaozn0oHpZS91ZqwVDLjkXsmIIiKBKfk0-nX1PMfycMOVmcMmi92bEMKUGtCo1gFpAfQZtDClF7JtTdIOJcwOseYql-T-WZSyacyyL9v1lydQub3xWXnJYgI8XwCRrfB_NaF165qSuFdOc_wNWFJzJ</recordid><startdate>20050719</startdate><enddate>20050719</enddate><creator>EL-SAWY, Tarek</creator><creator>BELPERIO, John A</creator><creator>STRIETER, Robert M</creator><creator>REMICK, Daniel G</creator><creator>FAIRCHILD, Robert L</creator><general>Lippincott Williams & Wilkins</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></search><sort><creationdate>20050719</creationdate><title>Inhibition of polymorphonuclear leukocyte-mediated graft damage synergizes with short-term costimulatory blockade to prevent cardiac allograft rejection</title><author>EL-SAWY, Tarek ; BELPERIO, John A ; STRIETER, Robert M ; REMICK, Daniel G ; FAIRCHILD, Robert L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-51106e754fd4d5b4f64bceb41d7b6ca931f17f6869dcc940e36334650e1ee1723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Abatacept</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>CD40 Ligand - physiology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cytokines - biosynthesis</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Endothelial Cells - physiology</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival</topic><topic>Heart</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Heart Transplantation - immunology</topic><topic>Immunoconjugates - pharmacology</topic><topic>Immunologic Memory</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Neutrophil Infiltration</topic><topic>Neutrophils - physiology</topic><topic>Receptors, Interleukin-8B - antagonists & inhibitors</topic><topic>Receptors, Interleukin-8B - physiology</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EL-SAWY, Tarek</creatorcontrib><creatorcontrib>BELPERIO, John A</creatorcontrib><creatorcontrib>STRIETER, Robert M</creatorcontrib><creatorcontrib>REMICK, Daniel G</creatorcontrib><creatorcontrib>FAIRCHILD, Robert L</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><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EL-SAWY, Tarek</au><au>BELPERIO, John A</au><au>STRIETER, Robert M</au><au>REMICK, Daniel G</au><au>FAIRCHILD, Robert L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of polymorphonuclear leukocyte-mediated graft damage synergizes with short-term costimulatory blockade to prevent cardiac allograft rejection</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2005-07-19</date><risdate>2005</risdate><volume>112</volume><issue>3</issue><spage>320</spage><epage>331</epage><pages>320-331</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The early inflammatory response during reperfusion of cardiac allografts is initiated by the infiltration of polymorphonuclear leukocytes (PMNs) into the graft. The impact of early PMN infiltration on allograft rejection compared with long-term graft survival remains poorly understood.
We tested the role of CXCR2, the receptor for 2 PMN attractant chemokines, KC/CXCL1 and MIP-2/CXCL2, on intragraft inflammation and vascularized cardiac allograft rejection in a murine model. Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera-treated wild-type or from CXCR2(-/-) recipients. Adoptive transfer of alloantigen-primed T cells rapidly infiltrated and rejected allografts in control recipients, but T-cell infiltration was significantly decreased in recipients depleted of PMNs at transplantation. The influence of early PMN-mediated inflammation on the therapeutic efficacy of costimulatory blockade to prevent allograft rejection was tested. Short-term treatment of recipients with anti-CD154 mAb or CTLA-4 Ig induced modest prolongation of cardiac allograft survival. However, CD154 mAb or CTLA-4 Ig treatment, combined with either peritransplantation PMN depletion or antibodies specific for KC/CXCL1 plus MIP-2/CXCL2, prolonged cardiac allograft survival beyond 100 days.
Results suggest that strategies attenuating PMN-mediated tissue damage during reperfusion significantly improve the efficacy of short-term costimulatory blockade to prevent T-cell-mediated rejection of cardiac allografts.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>15998678</pmid><doi>10.1161/CIRCULATIONAHA.104.516708</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2005-07, Vol.112 (3), p.320-331 |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Abatacept Animals Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system CD40 Ligand - physiology CD8-Positive T-Lymphocytes - immunology Cytokines - biosynthesis Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Endothelial Cells - physiology Graft Rejection - prevention & control Graft Survival Heart Heart failure, cardiogenic pulmonary edema, cardiac enlargement Heart Transplantation - immunology Immunoconjugates - pharmacology Immunologic Memory Male Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL Neutrophil Infiltration Neutrophils - physiology Receptors, Interleukin-8B - antagonists & inhibitors Receptors, Interleukin-8B - physiology Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart Transplantation, Homologous |
| title | Inhibition of polymorphonuclear leukocyte-mediated graft damage synergizes with short-term costimulatory blockade to prevent cardiac allograft rejection |
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