Sökning: onr:"swepub:oai:DiVA.org:oru-111597" >
Post‐transplant upr...
-
Hårdstedt, Maria,1971-Uppsala universitet,Klinisk immunologi,Korsgren
(författare)
Post‐transplant upregulation of chemokine messenger RNA in non‐human primate recipients of intraportal pig islet xenografts
- Artikel/kapitelEngelska2005
Förlag, utgivningsår, omfång ...
-
John Wiley & Sons,2005
-
printrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:oru-111597
-
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-111597URI
-
https://doi.org/10.1111/j.1399-3089.2005.00228.xDOI
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-233185URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
BACKGROUND: We have previously shown that pig-to-primate intraportal islet xenografts reverse diabetes, escape hyperacute rejection, and undergo acute cellular rejection in non-immunosuppressed recipients. To gain a better understanding of mechanisms contributing to xenoislet rejection in non-human primates we examined gene expression in livers bearing islet xenografts in the first 72 h after transplantation.METHODS: Liver specimens were collected at sacrifice from seven non-immunosuppressed rhesus macaques at 12, 24, 48 and 72 h after intraportal porcine islet transplantation. Following total RNA extraction, mRNA was quantified using SYBR green real-time reverse transcription polymerase chain reaction (RT-PCR) for species-specific immune response genes. Data were analyzed using comparative cycle threshold (Ct) analysis, adjusted for specific primer-efficiencies and normalized to cyclophilin expression.RESULTS: Porcine insulin mRNA was detected in all liver samples. Cluster analysis revealed differential gene expression patterns at 12 and 24 h (early) compared with at 48 and 72 h (late) post-transplant. Gene expression patterns were associated with histological findings of predominantly neutrophils and only a few lymphocytes at 12 and 24 h and an increasing number of lymphocytes and macrophages at 48 and 72 h. Transcript levels of CXCR3 and its ligands, interferon-inducible protein 10 (IP-10) and monokine induced by IFN-gamma (Mig), significantly increased between early and late time points together with expression of MIP-1alpha, regulated on activation normal T expressed and secreted protein (RANTES) and MCP-1. CCR5 showed only a marginal, non-significant increase. Fas ligand, perforin and granzyme B transcripts were all elevated at 48 and 72 h post-transplant.CONCLUSIONS: Our data suggest that CXCR3, with ligands IP-10 and Mig, is involved in T cell recruitment in acute islet xenograft rejection in non-human primates. Upregulation of RANTES and MIP-1alpha transcripts in the absence of a significant CCR5 increase suggests a possible involvement of other chemokine receptors. MCP-1 expression is associated with T cell and macrophage infiltration. Elevated cytotoxic effector molecule expression (Fas ligand, perforin, granzyme B) indicates T-cell mediated graft destruction by cytotoxic and cytolytic mechanisms within 48 to 72 h after transplantation. These results identify the CXCR3-mediated chemoattractant pathway as an immunosuppressive target in pig-to-primate islet xenotransplantation.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Finnegan, Colleen P.Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN, USA
(författare)
-
Kirchhof, NicoleDiabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
(författare)
-
Hyland, Kendra A.Departmentof Veterinary and Biomedical Sciences, University ofMinnesota, St Paul, MN, USA
(författare)
-
Wijkstrom, MartinDiabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
(författare)
-
Murtaugh, Michael P.Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN, USA
(författare)
-
Hering, Bernhard J.Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
(författare)
-
Uppsala universitetKlinisk immunologi
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Xenotransplantation: John Wiley & Sons12:4, s. 293-3020908-665X1399-3089
Internetlänk
Hitta via bibliotek
Till lärosätets databas