Linked Life Data

12009948

Source:http://linkedlifedata.com/resource/pubmed/id/12009948

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-5-15
pubmed:abstractText
Porcine organs are rapidly rejected after transplantation into primate recipients due to the presence of preexisting immunoglobulins that bind to terminal galactose alpha1,3 galactose residues (alpha-galactosyl) present on porcine glycoproteins and glycolipids. Currently available immunosuppressive reagents have been largely ineffective at controlling the synthesis of these anti-Gal antibodies. Nonantigenic hapten polymers have been shown to be effective materials for blocking humoral immune responses in various model systems. We have developed a series of alpha-galactosyl glycoconjugate polymers and tested their ability to block anti-Gal antibody binding in vitro and in vivo. A galactose alpha1,3 galactose beta 1,4 GlcNAc trisaccharide free acid (TRFA) with a hexanoic acid spacer, containing five methylene groups and a carboxylic acid, was produced and coupled to a variety of polymeric backbones including dextran, branched poly(ethylene glycol) (PEG), and poly-L-lysine. The ability of monomeric TRFA and the alpha-galactosyl conjugates to block anti-Gal IgG and IgM binding was determined using a competition ELISA assay on defined HSA-Gal glycoconjugates and porcine microvascular endothelial cell substrates. We show that branched PEG carriers, with a TRFA sugar attached to each branch, exhibit enhanced antibody blocking ability compared to TRFA, but at higher target antigen densities these simple PEG conjugates are no more effective then an equivalent amount of TRFA in blocking anti-Gal IgM antibody interactions. In contrast, polymers of the branched PEG conjugates and linear conjugates made using dextran and poly-L-lysine were 2000 to 70000-fold more effective inhibitors of anti-Gal antibodies. In a study using nonhuman primates, a single dose infusion of polymeric PEG or dextran glycoconjugates dramatically reduced the level of circulating anti-Gal antibodies in cynomologus monkeys for at least 72 h. Glycoconjugates similar to these might be useful both to block anti-Gal interactions in vivo and to specifically control the induced anti-Gal immune response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1043-1802
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
571-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12009948-Animals, pubmed-meshheading:12009948-Antibodies, Blocking, pubmed-meshheading:12009948-Chromatography, High Pressure Liquid, pubmed-meshheading:12009948-Cytotoxicity, Immunologic, pubmed-meshheading:12009948-Endothelium, Vascular, pubmed-meshheading:12009948-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:12009948-Galactose, pubmed-meshheading:12009948-Glycoconjugates, pubmed-meshheading:12009948-Graft Rejection, pubmed-meshheading:12009948-Humans, pubmed-meshheading:12009948-Immunoglobulin M, pubmed-meshheading:12009948-Macaca fascicularis, pubmed-meshheading:12009948-Mass Spectrometry, pubmed-meshheading:12009948-Papio, pubmed-meshheading:12009948-Polyethylene Glycols, pubmed-meshheading:12009948-Swine, pubmed-meshheading:12009948-Transplantation, Heterologous, pubmed-meshheading:12009948-Trisaccharides
pubmed:articleTitle
Evaluation of different alpha-Galactosyl glycoconjugates for use in xenotransplantation.
pubmed:affiliation
Nextran Inc., 303B College Road, Princeton, New Jersey, USA. gbyrne@nextran.com
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't