Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/13560
Full metadata record
DC FieldValueLanguage
dc.contributor.authorOsman, Nen
dc.contributor.authorMcKenzie, Ian F Cen
dc.contributor.authorOstenried, Ken
dc.contributor.authorIoannou, Y Aen
dc.contributor.authorDesnick, R Jen
dc.contributor.authorSandrin, Mauro Sen
dc.date.accessioned2015-05-16T03:26:20Z
dc.date.available2015-05-16T03:26:20Z
dc.date.issued1997-12-23en
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America; 94(26): 14677-82en
dc.identifier.govdoc9405672en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/13560en
dc.description.abstractHyperacute rejection of pig organs by humans involves the interaction of Galalpha(1,3)Gal with antibodies and complement. Strategies to reduce the amount of xenoantigen Galalpha(1,3)Gal were investigated by overexpression of human lysosomal alpha-galactosidase in cultured porcine cells and transgenic mice. The overexpression of human alpha-galactosidase in cultured porcine endothelial cells and COS cells resulted in a 30-fold reduction of cell surface Galalpha(1,3)Gal and a 10-fold reduction in cell reactivity with natural human antibodies. Splenocytes from transgenic mice overexpressing human alpha-galactosidase showed only a 15-25% reduction in binding to natural human anti-Galalpha(1,3)Gal antibodies; however, this decrease was functionally significant as demonstrated by reduced susceptibility to human antibody-mediated lysis. However, because there is residual Galalpha(1,3)Gal and degalactosylation results in the exposure of N-acetyllactosamine residues and potential new xenoepitopes, using alpha-galactosidase alone is unlikely to overcome hyperacute rejection. We previously reported that mice overexpressing human alpha1,2-fucosyltransferase as a transgene had approximately 90% reduced Galalpha(1,3)Gal levels due to masking of the xenoantigen by fucosylation; we evaluated the effect of overexpressing alpha-galactosidase and alpha1,2-fucosyltransferase on Galalpha(1,3)Gal levels. Galalpha(1, 3)Gal-positive COS cells expressing alpha1,3-galactosyltransferase, alpha1,2-fucosyltransferase, and alpha-galactosidase showed negligible cell surface staining and were not susceptible to lysis by human serum containing antibody and complement. Thus, alpha1, 2-fucosyltransferase and alpha-galactosidase effectively reduced the expression of Galalpha(1,3)Gal on the cell surface and could be used to produce transgenic pigs with negligible levels of cell surface Galalpha(1,3)Gal, thereby having no reactivity with human serum and improving graft survival.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherFucosyltransferases.genetics.immunologyen
dc.subject.otherGene Expression Regulationen
dc.subject.otherGene Transfer Techniquesen
dc.subject.otherGraft Rejection.genetics.immunologyen
dc.subject.otherHumansen
dc.subject.otherMiceen
dc.subject.otherMice, Transgenicen
dc.subject.otherOrgan Transplantationen
dc.subject.otherSwineen
dc.subject.otherTransplantation, Heterologousen
dc.subject.otherTrisaccharides.genetics.immunologyen
dc.subject.otheralpha-Galactosidase.genetics.immunologyen
dc.titleCombined transgenic expression of alpha-galactosidase and alpha1,2-fucosyltransferase leads to optimal reduction in the major xenoepitope Galalpha(1,3)Gal.en
dc.typeJournal Articleen
dc.identifier.journaltitleProceedings of the National Academy of Sciences of the United States of Americaen
dc.identifier.affiliationMolecular Immunogenetics Laboratory, Austin Research Institute, Austin Hospital, Heidelberg Victoria 3084 Australiaen
dc.description.pages14677-82en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/9405672en
dc.type.austinJournal Articleen
local.name.researcherSandrin, Mauro S
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptSurgery (University of Melbourne)-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

2
checked on Mar 28, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.