Regulated and endothelial cell-specific expression of Fas ligand : An in vitro model for a strategy aiming at inhibiting xenograft rejection
Immunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection. We proposed that endothelial cells that ar...
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| Veröffentlicht in: | Transplantation 1998-11, Vol.66 (9), p.1126-1131 |
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| container_title | Transplantation |
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| creator | HIEN TRAN, T GREY, S ANRATHER, J STEINHÄUSLIN, F BACH, F. H WINKLER, H |
| description | Immunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL.
Based on the tetracycline-regulated expression system, constructs were designed that allow endothelial cell-specific and regulated expression of FasL by placing the tetracycline-dependent transactivator under control of the murine intercellular adhesion molecule-2 promoter.
Primary bovine endothelial cells transfected with FasL efficiently killed Fas-expressing cells in a regulated manner. Not only Fas-positive cell lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells.
This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation. |
| doi_str_mv | 10.1097/00007890-199811150-00002 |
| format | Article |
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Based on the tetracycline-regulated expression system, constructs were designed that allow endothelial cell-specific and regulated expression of FasL by placing the tetracycline-dependent transactivator under control of the murine intercellular adhesion molecule-2 promoter.
Primary bovine endothelial cells transfected with FasL efficiently killed Fas-expressing cells in a regulated manner. Not only Fas-positive cell lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells.
This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/00007890-199811150-00002</identifier><identifier>PMID: 9825805</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Animal cells ; Animals ; Aorta - cytology ; Apoptosis ; Biological and medical sciences ; Biotechnology ; Cattle ; Cell Death ; Endothelium, Vascular - cytology ; Endothelium, Vascular - metabolism ; Eukaryotic cell cultures ; Fas Ligand Protein ; Fundamental and applied biological sciences. Psychology ; Genetical aspects ; Graft Rejection - prevention & control ; Humans ; Jurkat Cells - physiology ; Leukocytes, Mononuclear - cytology ; Membrane Glycoproteins - biosynthesis ; Methods. Procedures. Technologies ; Models, Immunological</subject><ispartof>Transplantation, 1998-11, Vol.66 (9), p.1126-1131</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1599978$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9825805$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HIEN TRAN, T</creatorcontrib><creatorcontrib>GREY, S</creatorcontrib><creatorcontrib>ANRATHER, J</creatorcontrib><creatorcontrib>STEINHÄUSLIN, F</creatorcontrib><creatorcontrib>BACH, F. H</creatorcontrib><creatorcontrib>WINKLER, H</creatorcontrib><title>Regulated and endothelial cell-specific expression of Fas ligand : An in vitro model for a strategy aiming at inhibiting xenograft rejection</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Immunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL.
Based on the tetracycline-regulated expression system, constructs were designed that allow endothelial cell-specific and regulated expression of FasL by placing the tetracycline-dependent transactivator under control of the murine intercellular adhesion molecule-2 promoter.
Primary bovine endothelial cells transfected with FasL efficiently killed Fas-expressing cells in a regulated manner. Not only Fas-positive cell lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells.
This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation.</description><subject>Animal cells</subject><subject>Animals</subject><subject>Aorta - cytology</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cattle</subject><subject>Cell Death</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Eukaryotic cell cultures</subject><subject>Fas Ligand Protein</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetical aspects</subject><subject>Graft Rejection - prevention & control</subject><subject>Humans</subject><subject>Jurkat Cells - physiology</subject><subject>Leukocytes, Mononuclear - cytology</subject><subject>Membrane Glycoproteins - biosynthesis</subject><subject>Methods. Procedures. Technologies</subject><subject>Models, Immunological</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkN9qFTEQxoNY6rH6CEIuxLvV_NlsEu9KsVUoCEWvD5Ps7DYlm6xJjrTv4EN3Dx68dW6Gme83H8xHCOXsI2dWf2JbaWNZx601nHPFuuNKvCA7rmTfDcywl2THWM87LqV-RV7X-rARSmp9Ts6tEcowtSN_7nA-RGg4UkgjxTTmdo8xQKQeY-zqij5MwVN8XAvWGnKieaLXUGkM8_HkM71MNCT6O7SS6ZJHjHTKhQKtrWzG8xOFsIQ0U2gbdx9caMfpEVOeC0yNFnxA3zbnN-Rsgljx7alfkJ_XX35cfe1uv998u7q87VYxDK2TDmzveqXEgIw521vpPU4OJgQrrB6lYMiFBwlOShQcOAAXTnHbG-idvCAf_vquJf86YG37JdTju5AwH-pesy0-pth_Qa65GYzRG_juBB7cguN-LWGB8rQ_5bzp7086VA9xKpB8qP8wrqy12shn3TuPog</recordid><startdate>19981115</startdate><enddate>19981115</enddate><creator>HIEN TRAN, T</creator><creator>GREY, S</creator><creator>ANRATHER, J</creator><creator>STEINHÄUSLIN, F</creator><creator>BACH, F. 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H ; WINKLER, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p266t-3ba94b45526e00b9493ccefbafea9297d320e12ca3ab33e21a1aa12b51948a4b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animal cells</topic><topic>Animals</topic><topic>Aorta - cytology</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cattle</topic><topic>Cell Death</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Eukaryotic cell cultures</topic><topic>Fas Ligand Protein</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetical aspects</topic><topic>Graft Rejection - prevention & control</topic><topic>Humans</topic><topic>Jurkat Cells - physiology</topic><topic>Leukocytes, Mononuclear - cytology</topic><topic>Membrane Glycoproteins - biosynthesis</topic><topic>Methods. Procedures. Technologies</topic><topic>Models, Immunological</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HIEN TRAN, T</creatorcontrib><creatorcontrib>GREY, S</creatorcontrib><creatorcontrib>ANRATHER, J</creatorcontrib><creatorcontrib>STEINHÄUSLIN, F</creatorcontrib><creatorcontrib>BACH, F. 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H</au><au>WINKLER, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulated and endothelial cell-specific expression of Fas ligand : An in vitro model for a strategy aiming at inhibiting xenograft rejection</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>1998-11-15</date><risdate>1998</risdate><volume>66</volume><issue>9</issue><spage>1126</spage><epage>1131</epage><pages>1126-1131</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Immunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL.
Based on the tetracycline-regulated expression system, constructs were designed that allow endothelial cell-specific and regulated expression of FasL by placing the tetracycline-dependent transactivator under control of the murine intercellular adhesion molecule-2 promoter.
Primary bovine endothelial cells transfected with FasL efficiently killed Fas-expressing cells in a regulated manner. Not only Fas-positive cell lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells.
This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>9825805</pmid><doi>10.1097/00007890-199811150-00002</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-1337 |
| ispartof | Transplantation, 1998-11, Vol.66 (9), p.1126-1131 |
| issn | 0041-1337 1534-6080 |
| language | eng |
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| source | MEDLINE; Journals@Ovid Ovid Autoload |
| subjects | Animal cells Animals Aorta - cytology Apoptosis Biological and medical sciences Biotechnology Cattle Cell Death Endothelium, Vascular - cytology Endothelium, Vascular - metabolism Eukaryotic cell cultures Fas Ligand Protein Fundamental and applied biological sciences. Psychology Genetical aspects Graft Rejection - prevention & control Humans Jurkat Cells - physiology Leukocytes, Mononuclear - cytology Membrane Glycoproteins - biosynthesis Methods. Procedures. Technologies Models, Immunological |
| title | Regulated and endothelial cell-specific expression of Fas ligand : An in vitro model for a strategy aiming at inhibiting xenograft rejection |
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