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Post‐transplant upr...
Post‐transplant upregulation of chemokine messenger RNA in non‐human primate recipients of intraportal pig islet xenografts
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- Hårdstedt, Maria, 1971- (författare)
- Uppsala universitet,Klinisk immunologi,Korsgren
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- Finnegan, Colleen P. (författare)
- Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN, USA
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- Kirchhof, Nicole (författare)
- Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
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- Hyland, Kendra A. (författare)
- Departmentof Veterinary and Biomedical Sciences, University ofMinnesota, St Paul, MN, USA
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- Wijkstrom, Martin (författare)
- Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
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- Murtaugh, Michael P. (författare)
- Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN, USA
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- Hering, Bernhard J. (författare)
- Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
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(creator_code:org_t)
- John Wiley & Sons, 2005
- 2005
- Engelska.
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Ingår i: Xenotransplantation. - : John Wiley & Sons. - 0908-665X .- 1399-3089. ; 12:4, s. 293-302
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
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- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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