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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-10-9
pubmed:abstractText
Endothelial cells (EC) are primary targets of the recipient's immune response to transplanted organs and constitutively express Fas (CD95) ligand (FasL) on their surface. We investigated the role of porcine FasL in the generation of the human anti-pig response in vitro. Porcine aortic endothelial cells (PAEC) lysed a Fas+ human T-cell line, Jurkat. Anti-human Fas monoclonal antibody (mAb) specifically inhibited this killing in a dose-dependent manner, suggesting that porcine FasL recognizes and binds human Fas to induce apoptosis of human Fas+ cells. We next cloned porcine FasL, identifying an open reading frame of 849 base pairs predicting a protein of 282 amino acids. The predicted amino acid sequence was 85, 76, and 75% homologous to the predicted amino acid sequences of human, mouse, and rat, respectively, and found that PAEC expressed both FasL mRNA and protein. Transient transfection was used to increase or induce porcine FasL expression in PAEC or COS-7 cells. Transfection of PAEC with a plasmid encoding porcine FasL increased their ability to induce apoptosis in Jurkat cells, fresh human T cells activated with IL-2 and anti-CD3, and fresh IL-2-activated human (natural killer) NK cells. Moreover, porcine Fas L-transfected COS-7 cells induced significant apoptosis in Jurkat cells compared with that induced by mock-transfected COS-7 cells. Finally, the overexpression of porcine FasL in PAEC reduced their susceptibility as target cells to lysis by activated human NK or T cells. These findings suggest that porcine FasL overexpression in EC of vascularized xenografts may provide protection from cellular xenograft rejection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0908-665X
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
410-21
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12371937-Animals, pubmed-meshheading:12371937-Antibodies, Monoclonal, pubmed-meshheading:12371937-Aorta, pubmed-meshheading:12371937-Apoptosis, pubmed-meshheading:12371937-Base Sequence, pubmed-meshheading:12371937-COS Cells, pubmed-meshheading:12371937-Cloning, Molecular, pubmed-meshheading:12371937-Endothelium, Vascular, pubmed-meshheading:12371937-Fas Ligand Protein, pubmed-meshheading:12371937-Gene Expression, pubmed-meshheading:12371937-Graft Rejection, pubmed-meshheading:12371937-Humans, pubmed-meshheading:12371937-Jurkat Cells, pubmed-meshheading:12371937-Killer Cells, Natural, pubmed-meshheading:12371937-Membrane Glycoproteins, pubmed-meshheading:12371937-Molecular Sequence Data, pubmed-meshheading:12371937-Sequence Homology, Amino Acid, pubmed-meshheading:12371937-T-Lymphocytes, pubmed-meshheading:12371937-Transfection, pubmed-meshheading:12371937-Transplantation, Heterologous, pubmed-meshheading:12371937-Transplantation Immunology
pubmed:year
2002
pubmed:articleTitle
Cloning and potential utility of porcine Fas ligand: overexpression in porcine endothelial cells protects them from attack by human cytolytic cells.
pubmed:affiliation
Laboratory of Immunology and Virology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article