Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-3-28
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-924X
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1067-73
pubmed:dateRevised
2007-12-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Regulation of natural killer cell-mediated swine endothelial cell lysis through genetic remodeling of a glycoantigen.
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.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't