Evidence for Galalpha(1-3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems
| Autor: | David H. Joziasse, Ruurdtje Hoekstra, Thomas M. van Gulik, Maarten-Paul van de Kerkhove, Tanja Deurholt, Albert C.W.A. van Wijk, Anja Roos, Menno R. Germans, Robert A. F. M. Chamuleau |
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| Přispěvatelé: | Neurosurgery, Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Tytgat Institute for Liver and Intestinal Research |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Graft Rejection
Pathology medicine.medical_specialty medicine.medical_treatment Sus scrofa Transplantation Heterologous Fluorescent Antibody Technique Biology Liver transplantation Immunofluorescence Disaccharides Antibodies law.invention Flow cytometry Bioreactors law medicine Animals Humans RNA Messenger Cells Cultured Hepatology medicine.diagnostic_test Graft Survival Bioartificial liver device Liver Failure Acute Flow Cytometry Galactosyltransferases Molecular biology Liver Artificial Reverse transcription polymerase chain reaction medicine.anatomical_structure Cell culture Hepatocyte biology.protein Hepatocytes Antibody |
| Zdroj: | Journal of hepatology, 42(4), 541-547. Elsevier |
| ISSN: | 0168-8278 |
| Popis: | BACKGROUND/AIMS: To bridge acute liver failure (ALF) patients to orthotopic liver transplantation, several bioartificial liver (BAL) systems have been developed. The bio-component of most BAL systems consists mainly of porcine hepatocytes. Plasma or blood of ALF patients is perfused through the BAL thereby contacting porcine hepatocytes. Xenogeneic BAL systems may suffer from hyperacute rejection similar to whole-organ xenotransplants. Hyperacute rejection is mediated by antibodies directed against Galalpha(1-3)Gal, a carbohydrate structure present on most mammalian cells. Galalpha(1-3)Gal is produced by the enzyme alpha1,3-galactosyltansferase (alphaGal-T). Conflicting data have been published concerning Galalpha(1-3)Gal expression on hepatocytes in intact porcine liver. We investigated whether isolated porcine hepatocytes express Galalpha(1-3)Gal. METHODS: Immunofluorescence, flow cytometry, RT-PCR and enzyme activity assays were performed on freshly isolated and cultured porcine hepatocytes and liver biopsies. Anti-Galalpha(1-3)Gal antibodies were measured in plasma from patients treated with BAL by ELISA. RESULTS: Isolated porcine hepatocytes express (alphaGal-T) at low levels and Galalpha(1-3)Gal is present in low quantities on these cells, in contrast to hepatocytes in situ. Furthermore, IgG and IgM anti-Galalpha(1-3)Gal are depleted from the plasma of ALF patients during BAL treatment. CONCLUSIONS: Isolation and culture of porcine hepatocytes induce Galalpha(1-3)Gal expression, which may elicit immunological responses potentially compromising BAL functionality |
| Databáze: | OpenAIRE |
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