Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Structural characterizati… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Structural characterization of alpha1,3-galactosyltransferase knockout pig heart and kidney glycolipids and their reactivity with human and baboon antibodies.

Artikel i vetenskaplig tidskrift
Författare Mette Diswall
Jonas Ångström
Hasse Karlsson
Carol J Phelps
David Ayares
Susann Teneberg
Michael Breimer
Publicerad i Xenotransplantation
Volym 17
Nummer/häfte 1
Sidor 48-60
ISSN 1399-3089
Publiceringsår 2010
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för kirurgi
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 48-60
Språk en
Länkar dx.doi.org/10.1111/j.1399-3089.2009...
Ämnesord Animals, Animals, Genetically Modified, Antibodies, blood, immunology, Antigens, immunology, Carbohydrate Sequence, Chromatography, Thin Layer, Galactosyltransferases, genetics, metabolism, Glycolipids, chemistry, immunology, Humans, Kidney, chemistry, Mass Spectrometry, Molecular Sequence Data, Myocardium, chemistry, Nuclear Magnetic Resonance, Biomolecular, Papio, immunology, Swine, genetics, immunology
Ämneskategorier Kemi

Sammanfattning

BACKGROUND: alpha1,3-galactosyltranferase knockout (GalT-KO) pigs have been established to avoid hyperacute rejection in GalT-KO pig-to-human xenotransplantation. GalT-KO pig heart and kidney glycolipids were studied focusing on elimination of Gal-antigens and whether novel antigens would appear. Non-human primates are used as pre-clinical transplantation experimental models. Therefore, sera from baboons transplanted with GalT-KO hearts were compared with human serum regarding reactivity with pig glycolipids. METHODS: Neutral and acidic glycolipids were isolated from GalT-KO and WT pig hearts and kidneys. Glycolipid immune reactivity was tested on TLC plates using human affinity-purified anti-Gal Ig, anti-blood group monoclonal antibodies, lectins, and human serum as well as baboon serum collected before and after GalT-KO pig heart transplantations. Selected glycolipid fractions, isolated by HPLC, were structurally characterized by mass spectrometry and proton NMR spectroscopy. RESULTS: GalT-KO heart and kidney lacked alpha3Gal-terminated glycolipids completely. Levels of uncapped N-acetyllactosamine precursor compounds, blood group H type 2 core chain compounds, the P1 antigen and the x(2) antigen were increased. Human serum antibodies reacted with Gal-antigens and N-glycolylneuraminic acid (NeuGc) in WT organs of which only the NeuGc reactivity remained in the GalT-KO tissues. A clear difference in reactivity between baboon and human antibodies with pig glycolipids was found. This was most pronounced for acidic, not yet identified, compounds in GalT-KO organs which were less abundant or lacking in the corresponding WT tissues. CONCLUSIONS: GalT-KO pig heart and kidney completely lacked Gal glycolipid antigens whilst glycolipids synthesized by competing pathways were increased. Baboon and human serum antibodies showed a different reactivity pattern to pig glycolipid antigens indicating that non-human primates have limitations as a human pre-clinical model for immune rejection studies.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?