Source:http://linkedlifedata.com/resource/pubmed/id/10578058
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2000-3-28
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pubmed:abstractText |
The effect of remodeling of a glycoantigen such as the alpha-Gal epitope, Galalpha1,3Galbeta1,4GlcNAc-R, by the introduction of glycosyltransferase genes on natural killer (NK) cell-mediated direct cytotoxicity was investigated using human peripheral blood mononuclear cells (PBMC) or an NK-like cell line, YT cells, as an effector, and swine endothelial cells (SEC) as a target. Several SEC transfectants were established by transfection with the genes for beta1,4-N-acetylglucosaminyltransferase III, alpha2, 3-sialyltransferase and alpha1,2-fucosyltransferase. These transfections led to dramatic reductions in both direct and indirect NK cell-mediated cytotoxicity, by 72-94% in the case of PBMC and 27-72% in that of YT cells, in addition to an effective reduction in xenoantigenicity, which is substantially caused by the alpha-Gal epitope, to human natural antibodies. The NK cell-mediated direct cytotoxicity was remarkably blocked by an anti-alpha-Gal epitope monoclonal antibody or GSI lectin which preferentially binds to the epitope. Furthermore, treatment of the parental cells with alpha-galactosidase resulted in a significant reduction in cytotoxicity. These results suggest that the alpha-Gal epitope is involved not only in hyperacute rejection and acute vascular rejection, but also in NK cell-mediated direct cytotoxicity. Thus, the genetic remodeling of the alpha-Gal epitope and probably other glycoantigens as well can be expected to represent a new approach for overcoming not only indirect but also direct immunity to xenografts.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glycosyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Griffonia simplicifolia lectins,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins,
http://linkedlifedata.com/resource/pubmed/chemical/Plant Lectins,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Galactosidase
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-924X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1067-73
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pubmed:dateRevised |
2007-12-19
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pubmed:meshHeading |
pubmed-meshheading:10578058-Animals,
pubmed-meshheading:10578058-Endothelium,
pubmed-meshheading:10578058-Flow Cytometry,
pubmed-meshheading:10578058-Glycosyltransferases,
pubmed-meshheading:10578058-Humans,
pubmed-meshheading:10578058-Killer Cells, Natural,
pubmed-meshheading:10578058-Lectins,
pubmed-meshheading:10578058-Mice,
pubmed-meshheading:10578058-Plant Lectins,
pubmed-meshheading:10578058-Swine,
pubmed-meshheading:10578058-Transfection,
pubmed-meshheading:10578058-alpha-Galactosidase
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pubmed:year |
1999
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pubmed:articleTitle |
Regulation of natural killer cell-mediated swine endothelial cell lysis through genetic remodeling of a glycoantigen.
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pubmed:affiliation |
Division of Organ Transplantation, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka University Medical School, Suita, Osaka, 565-0871, Japan. miyagawa@orgtrp.med.osaka-u ac.jp.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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