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Display of fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection
Fas ligand (FasL) is a potent death-inducing molecule with important functions in immune homeostasis and tolerance to self-antigens. The complex biological activities of FasL and its inefficient expression using conventional gene transfer approaches limit its use for immunomodulation to prevent allo...
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| Published in: | Circulation (New York, N.Y.) N.Y.), 2003-03, Vol.107 (11), p.1525-1531 |
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| cites | cdi_FETCH-LOGICAL-c467t-7f55d7878dbb4c4df28e68cc35e760a7750f55289378eda29c1efe115a7487df3 |
| container_end_page | 1531 |
| container_issue | 11 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | ASKENASY, Nadir YOLCU, Esma S ZHILIANG WANG SHIRWAN, Haval |
| description | Fas ligand (FasL) is a potent death-inducing molecule with important functions in immune homeostasis and tolerance to self-antigens. The complex biological activities of FasL and its inefficient expression using conventional gene transfer approaches limit its use for immunomodulation to prevent allograft rejection. We have recently generated a chimeric FasL with core streptavidin (SA-FasL) with potent apoptotic activity and designed a novel approach to display it on the surface of several cell types via biotinylation. We herein tested whether SA-FasL can also be displayed on vascular endothelial cells in the heart and examined its effect on graft survival after transplantation into syngeneic and allogeneic hosts.
SA-FasL was efficiently displayed on the vasculature of BALB/c hearts with a half-life of 9 days in vivo. Transplantation of hearts displaying SA-FasL into syngeneic hosts resulted in indefinite graft survival without detectable toxicity to the grafts and hosts. In contrast, transplantation of allogeneic C57BL/10 hearts displaying SA-FasL into BALB/c recipients resulted in graft rejection, but in a delayed fashion as compared with control hearts (mean survival time=17.4+/-5 versus 9.6+/-1 days). Allograft survival was further extended to 21+/-2.6 and 24+/-3 days (P |
| doi_str_mv | 10.1161/01.CIR.0000064893.96179.7E |
| format | article |
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SA-FasL was efficiently displayed on the vasculature of BALB/c hearts with a half-life of 9 days in vivo. Transplantation of hearts displaying SA-FasL into syngeneic hosts resulted in indefinite graft survival without detectable toxicity to the grafts and hosts. In contrast, transplantation of allogeneic C57BL/10 hearts displaying SA-FasL into BALB/c recipients resulted in graft rejection, but in a delayed fashion as compared with control hearts (mean survival time=17.4+/-5 versus 9.6+/-1 days). Allograft survival was further extended to 21+/-2.6 and 24+/-3 days (P<0.05) by intravenous treatment of graft recipients with 1 dose of SA-FasL-decorated donor splenocytes on days 2 and 6 after transplantation, respectively.
This study shows for the first time that exogenous proteins can be displayed on the endothelium of solid organs for therapeutic purposes. This approach provides a convenient and rapid means of displaying exogenous proteins on the surface of cells, tissues, and solid organs, with broad research and therapeutic implications.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.0000064893.96179.7E</identifier><identifier>PMID: 12654611</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Biotinylation ; Cell Movement ; Cell Transplantation ; Coronary Vessels - cytology ; Endothelium, Vascular - chemistry ; Fas Ligand Protein ; Graft Rejection - immunology ; Graft Rejection - pathology ; Graft Rejection - therapy ; Graft Survival ; Heart Transplantation - immunology ; Heart Transplantation - pathology ; Kinetics ; Medical sciences ; Membrane Glycoproteins - genetics ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Neutrophils - immunology ; Recombinant Fusion Proteins - analysis ; Spleen - cytology ; Streptavidin - genetics ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart ; Transplantation Tolerance ; Transplantation, Homologous</subject><ispartof>Circulation (New York, N.Y.), 2003-03, Vol.107 (11), p.1525-1531</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Mar 25 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-7f55d7878dbb4c4df28e68cc35e760a7750f55289378eda29c1efe115a7487df3</citedby><cites>FETCH-LOGICAL-c467t-7f55d7878dbb4c4df28e68cc35e760a7750f55289378eda29c1efe115a7487df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14672198$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12654611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ASKENASY, Nadir</creatorcontrib><creatorcontrib>YOLCU, Esma S</creatorcontrib><creatorcontrib>ZHILIANG WANG</creatorcontrib><creatorcontrib>SHIRWAN, Haval</creatorcontrib><title>Display of fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Fas ligand (FasL) is a potent death-inducing molecule with important functions in immune homeostasis and tolerance to self-antigens. The complex biological activities of FasL and its inefficient expression using conventional gene transfer approaches limit its use for immunomodulation to prevent allograft rejection. We have recently generated a chimeric FasL with core streptavidin (SA-FasL) with potent apoptotic activity and designed a novel approach to display it on the surface of several cell types via biotinylation. We herein tested whether SA-FasL can also be displayed on vascular endothelial cells in the heart and examined its effect on graft survival after transplantation into syngeneic and allogeneic hosts.
SA-FasL was efficiently displayed on the vasculature of BALB/c hearts with a half-life of 9 days in vivo. Transplantation of hearts displaying SA-FasL into syngeneic hosts resulted in indefinite graft survival without detectable toxicity to the grafts and hosts. In contrast, transplantation of allogeneic C57BL/10 hearts displaying SA-FasL into BALB/c recipients resulted in graft rejection, but in a delayed fashion as compared with control hearts (mean survival time=17.4+/-5 versus 9.6+/-1 days). Allograft survival was further extended to 21+/-2.6 and 24+/-3 days (P<0.05) by intravenous treatment of graft recipients with 1 dose of SA-FasL-decorated donor splenocytes on days 2 and 6 after transplantation, respectively.
This study shows for the first time that exogenous proteins can be displayed on the endothelium of solid organs for therapeutic purposes. This approach provides a convenient and rapid means of displaying exogenous proteins on the surface of cells, tissues, and solid organs, with broad research and therapeutic implications.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biotinylation</subject><subject>Cell Movement</subject><subject>Cell Transplantation</subject><subject>Coronary Vessels - cytology</subject><subject>Endothelium, Vascular - chemistry</subject><subject>Fas Ligand Protein</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - pathology</subject><subject>Graft Rejection - therapy</subject><subject>Graft Survival</subject><subject>Heart Transplantation - immunology</subject><subject>Heart Transplantation - pathology</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy, Fluorescence</subject><subject>Neutrophils - immunology</subject><subject>Recombinant Fusion Proteins - analysis</subject><subject>Spleen - cytology</subject><subject>Streptavidin - genetics</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><subject>Transplantation Tolerance</subject><subject>Transplantation, Homologous</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNpFkF1LwzAUhoMobk7_goSBl61Nmo_WO5lTBwNB9DqcpUnp6NKZtIP9e1MdLDeBnOfN4X0QmpMsJUSQx4yki9Vnmo1HsKLM01IQWaZyeYGmhFOWMJ6Xl2ga52Uic0on6CaE7Yjnkl-jCaGCM0HIFNUvTdi3cMSdxRYCbpsaXIX3vutN43DnsAZfNaDxAYIeWugHb3AEAbvuYFq8M-DCmPamHseNqzG0bVd7sH183BrdN527RVcW2mDuTvcMfb8uvxbvyfrjbbV4XieaCdkn0nJeyUIW1WbDNKssLYwotM65kSIDKXkWCRo7y8JUQEtNjDWEcJCskJXNZ2j-_29s8DOY0KttN3gXVyoaWwuZMRGhp39I-y4Eb6za-2YH_qhIpkbFKiMqKlZnxepPsZLLGL4_bRg2O1OdoyenEXg4AdEYtNaD0004c7EoJWWR_wJ16IV2</recordid><startdate>20030325</startdate><enddate>20030325</enddate><creator>ASKENASY, Nadir</creator><creator>YOLCU, Esma S</creator><creator>ZHILIANG WANG</creator><creator>SHIRWAN, Haval</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope></search><sort><creationdate>20030325</creationdate><title>Display of fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection</title><author>ASKENASY, Nadir ; YOLCU, Esma S ; ZHILIANG WANG ; SHIRWAN, Haval</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-7f55d7878dbb4c4df28e68cc35e760a7750f55289378eda29c1efe115a7487df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biotinylation</topic><topic>Cell Movement</topic><topic>Cell Transplantation</topic><topic>Coronary Vessels - cytology</topic><topic>Endothelium, Vascular - chemistry</topic><topic>Fas Ligand Protein</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - pathology</topic><topic>Graft Rejection - therapy</topic><topic>Graft Survival</topic><topic>Heart Transplantation - immunology</topic><topic>Heart Transplantation - pathology</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Fluorescence</topic><topic>Neutrophils - immunology</topic><topic>Recombinant Fusion Proteins - analysis</topic><topic>Spleen - cytology</topic><topic>Streptavidin - genetics</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><topic>Transplantation Tolerance</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ASKENASY, Nadir</creatorcontrib><creatorcontrib>YOLCU, Esma S</creatorcontrib><creatorcontrib>ZHILIANG WANG</creatorcontrib><creatorcontrib>SHIRWAN, Haval</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 Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ASKENASY, Nadir</au><au>YOLCU, Esma S</au><au>ZHILIANG WANG</au><au>SHIRWAN, Haval</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Display of fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2003-03-25</date><risdate>2003</risdate><volume>107</volume><issue>11</issue><spage>1525</spage><epage>1531</epage><pages>1525-1531</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Fas ligand (FasL) is a potent death-inducing molecule with important functions in immune homeostasis and tolerance to self-antigens. The complex biological activities of FasL and its inefficient expression using conventional gene transfer approaches limit its use for immunomodulation to prevent allograft rejection. We have recently generated a chimeric FasL with core streptavidin (SA-FasL) with potent apoptotic activity and designed a novel approach to display it on the surface of several cell types via biotinylation. We herein tested whether SA-FasL can also be displayed on vascular endothelial cells in the heart and examined its effect on graft survival after transplantation into syngeneic and allogeneic hosts.
SA-FasL was efficiently displayed on the vasculature of BALB/c hearts with a half-life of 9 days in vivo. Transplantation of hearts displaying SA-FasL into syngeneic hosts resulted in indefinite graft survival without detectable toxicity to the grafts and hosts. In contrast, transplantation of allogeneic C57BL/10 hearts displaying SA-FasL into BALB/c recipients resulted in graft rejection, but in a delayed fashion as compared with control hearts (mean survival time=17.4+/-5 versus 9.6+/-1 days). Allograft survival was further extended to 21+/-2.6 and 24+/-3 days (P<0.05) by intravenous treatment of graft recipients with 1 dose of SA-FasL-decorated donor splenocytes on days 2 and 6 after transplantation, respectively.
This study shows for the first time that exogenous proteins can be displayed on the endothelium of solid organs for therapeutic purposes. This approach provides a convenient and rapid means of displaying exogenous proteins on the surface of cells, tissues, and solid organs, with broad research and therapeutic implications.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12654611</pmid><doi>10.1161/01.CIR.0000064893.96179.7E</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2003-03, Vol.107 (11), p.1525-1531 |
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| subjects | Animals Biological and medical sciences Biotinylation Cell Movement Cell Transplantation Coronary Vessels - cytology Endothelium, Vascular - chemistry Fas Ligand Protein Graft Rejection - immunology Graft Rejection - pathology Graft Rejection - therapy Graft Survival Heart Transplantation - immunology Heart Transplantation - pathology Kinetics Medical sciences Membrane Glycoproteins - genetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Microscopy, Fluorescence Neutrophils - immunology Recombinant Fusion Proteins - analysis Spleen - cytology Streptavidin - genetics Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart Transplantation Tolerance Transplantation, Homologous |
| title | Display of fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection |
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